diff --git a/source/blender/blenkernel/BKE_main.h b/source/blender/blenkernel/BKE_main.h
index daf394b811a..f4ac0cfd0e7 100644
--- a/source/blender/blenkernel/BKE_main.h
+++ b/source/blender/blenkernel/BKE_main.h
@@ -138,6 +138,13 @@ typedef struct Main {
    */
   bool is_locked_for_linking;
 
+  /**
+   * When set, indicates that an unrecoverable error/data corruption was detected.
+   * Should only be set by readfile code, and used by upper-level code (typically #setup_app_data)
+   * to cancel a file reading operation.
+   */
+  bool is_read_invalid;
+
   /**
    * True if this main is the 'GMAIN' of current Blender.
    *
diff --git a/source/blender/blenkernel/intern/blendfile.cc b/source/blender/blenkernel/intern/blendfile.cc
index 8f0e462cd27..a0ecb0c95b5 100644
--- a/source/blender/blenkernel/intern/blendfile.cc
+++ b/source/blender/blenkernel/intern/blendfile.cc
@@ -476,6 +476,13 @@ void BKE_blendfile_read_setup_ex(bContext *C,
                                  const bool startup_update_defaults,
                                  const char *startup_app_template)
 {
+  if (bfd->main->is_read_invalid) {
+    BKE_reports_prepend(reports->reports,
+                        "File could not be read, critical data corruption detected");
+    BLO_blendfiledata_free(bfd);
+    return;
+  }
+
   if (startup_update_defaults) {
     if ((params->skip_flags & BLO_READ_SKIP_DATA) == 0) {
       BLO_update_defaults_startup_blend(bfd->main, startup_app_template);
@@ -503,6 +510,10 @@ struct BlendFileData *BKE_blendfile_read(const char *filepath,
   }
 
   BlendFileData *bfd = BLO_read_from_file(filepath, eBLOReadSkip(params->skip_flags), reports);
+  if (bfd && bfd->main->is_read_invalid) {
+    BLO_blendfiledata_free(bfd);
+    bfd = nullptr;
+  }
   if (bfd) {
     handle_subversion_warning(bfd->main, reports);
   }
@@ -519,6 +530,10 @@ struct BlendFileData *BKE_blendfile_read_from_memory(const void *filebuf,
 {
   BlendFileData *bfd = BLO_read_from_memory(
       filebuf, filelength, eBLOReadSkip(params->skip_flags), reports);
+  if (bfd && bfd->main->is_read_invalid) {
+    BLO_blendfiledata_free(bfd);
+    bfd = nullptr;
+  }
   if (bfd) {
     /* Pass. */
   }
@@ -535,6 +550,10 @@ struct BlendFileData *BKE_blendfile_read_from_memfile(Main *bmain,
 {
   BlendFileData *bfd = BLO_read_from_memfile(
       bmain, BKE_main_blendfile_path(bmain), memfile, params, reports);
+  if (bfd && bfd->main->is_read_invalid) {
+    BLO_blendfiledata_free(bfd);
+    bfd = nullptr;
+  }
   if (bfd) {
     /* Removing the unused workspaces, screens and wm is useless here, setup_app_data will switch
      * those lists with the ones from old bmain, which freeing is much more efficient than
diff --git a/source/blender/blenloader/BLO_readfile.h b/source/blender/blenloader/BLO_readfile.h
index 8b5f9d10044..e28688b6bab 100644
--- a/source/blender/blenloader/BLO_readfile.h
+++ b/source/blender/blenloader/BLO_readfile.h
@@ -288,6 +288,26 @@ struct LinkNode *BLO_blendhandle_get_linkable_groups(BlendHandle *bh);
  */
 void BLO_blendhandle_close(BlendHandle *bh);
 
+/** Mark the given Main (and the 'root' local one in case of lib-split Mains) as invalid, and
+ * generate an error report containing given `message`. */
+void BLO_read_invalidate_message(BlendHandle *bh, struct Main *bmain, const char *message);
+
+/**
+ * BLI_assert-like macro to check a condition, and if `false`, fail the whole .blend reading
+ * process by marking the Main data-base as invalid, and returning provided `_ret_value`.
+ *
+ * NOTE: About usages:
+ *   - #BLI_assert should be used when the error is considered as a bug, but there is some code to
+ *     recover from it and produce a valid Main data-base.
+ *   - #BLO_read_assert_message should be used when the error is not considered as recoverable.
+ */
+#define BLO_read_assert_message(_check_expr, _ret_value, _bh, _bmain, _message) \
+  if (_check_expr) { \
+    BLO_read_invalidate_message((_bh), (_bmain), (_message)); \
+    return _ret_value; \
+  } \
+  (void)0
+
 /** \} */
 
 #define BLO_GROUP_MAX 32
diff --git a/source/blender/blenloader/intern/readblenentry.cc b/source/blender/blenloader/intern/readblenentry.cc
index 6b59ef87cec..c7884b3ae75 100644
--- a/source/blender/blenloader/intern/readblenentry.cc
+++ b/source/blender/blenloader/intern/readblenentry.cc
@@ -385,6 +385,13 @@ void BLO_blendhandle_close(BlendHandle *bh)
   blo_filedata_free(fd);
 }
 
+void BLO_read_invalidate_message(BlendHandle *bh, Main *bmain, const char *message)
+{
+  FileData *fd = reinterpret_cast<FileData *>(bh);
+
+  blo_readfile_invalidate(fd, bmain, message);
+}
+
 /**********/
 
 BlendFileData *BLO_read_from_file(const char *filepath,
diff --git a/source/blender/blenloader/intern/readfile.cc b/source/blender/blenloader/intern/readfile.cc
index 29730f7f10a..bbcc0d54c14 100644
--- a/source/blender/blenloader/intern/readfile.cc
+++ b/source/blender/blenloader/intern/readfile.cc
@@ -320,6 +320,10 @@ static void add_main_to_main(Main *mainvar, Main *from)
   ListBase *lbarray[INDEX_ID_MAX], *fromarray[INDEX_ID_MAX];
   int a;
 
+  if (from->is_read_invalid) {
+    mainvar->is_read_invalid = true;
+  }
+
   set_listbasepointers(mainvar, lbarray);
   a = set_listbasepointers(from, fromarray);
   while (a--) {
@@ -340,6 +344,9 @@ void blo_join_main(ListBase *mainlist)
   }
 
   while ((tojoin = mainl->next)) {
+    if (tojoin->is_read_invalid) {
+      mainl->is_read_invalid = true;
+    }
     add_main_to_main(mainl, tojoin);
     BLI_remlink(mainlist, tojoin);
     BKE_main_free(tojoin);
@@ -548,6 +555,21 @@ static Main *blo_find_main(FileData *fd, const char *filepath, const char *relab
   return m;
 }
 
+void blo_readfile_invalidate(FileData *fd, Main *bmain, const char *message)
+{
+  /* Tag given bmain, and 'root 'local' main one (in case given one is a library one) as invalid.
+   */
+  bmain->is_read_invalid = true;
+  for (; bmain->prev != nullptr; bmain = bmain->prev)
+    ;
+  bmain->is_read_invalid = true;
+
+  BLO_reportf_wrap(fd->reports,
+                   RPT_ERROR,
+                   "A critical error happened (the blend file is likely corrupted): %s",
+                   message);
+}
+
 /** \} */
 
 /* -------------------------------------------------------------------- */
@@ -3564,15 +3586,33 @@ static void do_versions(FileData *fd, Library *lib, Main *main)
               main->build_hash);
   }
 
-  blo_do_versions_pre250(fd, lib, main);
-  blo_do_versions_250(fd, lib, main);
-  blo_do_versions_260(fd, lib, main);
-  blo_do_versions_270(fd, lib, main);
-  blo_do_versions_280(fd, lib, main);
-  blo_do_versions_290(fd, lib, main);
-  blo_do_versions_300(fd, lib, main);
-  blo_do_versions_400(fd, lib, main);
-  blo_do_versions_cycles(fd, lib, main);
+  if (!main->is_read_invalid) {
+    blo_do_versions_pre250(fd, lib, main);
+  }
+  if (!main->is_read_invalid) {
+    blo_do_versions_250(fd, lib, main);
+  }
+  if (!main->is_read_invalid) {
+    blo_do_versions_260(fd, lib, main);
+  }
+  if (!main->is_read_invalid) {
+    blo_do_versions_270(fd, lib, main);
+  }
+  if (!main->is_read_invalid) {
+    blo_do_versions_280(fd, lib, main);
+  }
+  if (!main->is_read_invalid) {
+    blo_do_versions_290(fd, lib, main);
+  }
+  if (!main->is_read_invalid) {
+    blo_do_versions_300(fd, lib, main);
+  }
+  if (!main->is_read_invalid) {
+    blo_do_versions_400(fd, lib, main);
+  }
+  if (!main->is_read_invalid) {
+    blo_do_versions_cycles(fd, lib, main);
+  }
 
   /* WATCH IT!!!: pointers from libdata have not been converted yet here! */
   /* WATCH IT 2!: Userdef struct init see do_versions_userdef() above! */
@@ -3582,7 +3622,7 @@ static void do_versions(FileData *fd, Library *lib, Main *main)
   main->is_locked_for_linking = false;
 }
 
-static void do_versions_after_linking(Main *main, ReportList *reports)
+static void do_versions_after_linking(FileData *fd, Main *main)
 {
   CLOG_INFO(&LOG,
             2,
@@ -3595,13 +3635,27 @@ static void do_versions_after_linking(Main *main, ReportList *reports)
   /* Don't allow versioning to create new data-blocks. */
   main->is_locked_for_linking = true;
 
-  do_versions_after_linking_250(main);
-  do_versions_after_linking_260(main);
-  do_versions_after_linking_270(main);
-  do_versions_after_linking_280(main, reports);
-  do_versions_after_linking_290(main, reports);
-  do_versions_after_linking_300(main, reports);
-  do_versions_after_linking_cycles(main);
+  if (!main->is_read_invalid) {
+    do_versions_after_linking_250(main);
+  }
+  if (!main->is_read_invalid) {
+    do_versions_after_linking_260(main);
+  }
+  if (!main->is_read_invalid) {
+    do_versions_after_linking_270(main);
+  }
+  if (!main->is_read_invalid) {
+    do_versions_after_linking_280(fd, main);
+  }
+  if (!main->is_read_invalid) {
+    do_versions_after_linking_290(fd, main);
+  }
+  if (!main->is_read_invalid) {
+    do_versions_after_linking_300(fd, main);
+  }
+  if (!main->is_read_invalid) {
+    do_versions_after_linking_cycles(main);
+  }
 
   main->is_locked_for_linking = false;
 }
@@ -3810,6 +3864,9 @@ static BHead *read_userdef(BlendFileData *bfd, FileData *fd, BHead *bhead)
 static void blo_read_file_checks(Main *bmain)
 {
 #ifndef NDEBUG
+  BLI_assert(bmain->next == nullptr);
+  BLI_assert(!bmain->is_read_invalid);
+
   LISTBASE_FOREACH (wmWindowManager *, wm, &bmain->wm) {
     LISTBASE_FOREACH (wmWindow *, win, &wm->windows) {
       /* This pointer is deprecated and should always be nullptr. */
@@ -3914,6 +3971,10 @@ BlendFileData *blo_read_file_internal(FileData *fd, const char *filepath)
           bhead = read_libblock(fd, bfd->main, bhead, LIB_TAG_LOCAL, false, nullptr);
         }
     }
+
+    if (bfd->main->is_read_invalid) {
+      return bfd;
+    }
   }
 
   /* do before read_libraries, but skip undo case */
@@ -3927,6 +3988,10 @@ BlendFileData *blo_read_file_internal(FileData *fd, const char *filepath)
     }
   }
 
+  if (bfd->main->is_read_invalid) {
+    return bfd;
+  }
+
   if ((fd->skip_flags & BLO_READ_SKIP_DATA) == 0) {
     fd->reports->duration.libraries = PIL_check_seconds_timer();
     read_libraries(fd, &mainlist);
@@ -3953,7 +4018,7 @@ BlendFileData *blo_read_file_internal(FileData *fd, const char *filepath)
       blo_split_main(&mainlist, bfd->main);
       LISTBASE_FOREACH (Main *, mainvar, &mainlist) {
         BLI_assert(mainvar->versionfile != 0);
-        do_versions_after_linking(mainvar, fd->reports->reports);
+        do_versions_after_linking(fd, mainvar);
       }
       blo_join_main(&mainlist);
 
@@ -3963,6 +4028,10 @@ BlendFileData *blo_read_file_internal(FileData *fd, const char *filepath)
       BKE_main_id_refcount_recompute(bfd->main, false);
     }
 
+    if (bfd->main->is_read_invalid) {
+      return bfd;
+    }
+
     /* After all data has been read and versioned, uses LIB_TAG_NEW. Theoretically this should
      * not be calculated in the undo case, but it is currently needed even on undo to recalculate
      * a cache. */
@@ -4174,6 +4243,10 @@ static void expand_doit_library(void *fdhandle, Main *mainvar, void *old)
 {
   FileData *fd = static_cast<FileData *>(fdhandle);
 
+  if (mainvar->is_read_invalid) {
+    return;
+  }
+
   BHead *bhead = find_bhead(fd, old);
   if (bhead == nullptr) {
     return;
@@ -4432,7 +4505,16 @@ ID *BLO_library_link_named_part(Main *mainl,
                                 const LibraryLink_Params *params)
 {
   FileData *fd = (FileData *)(*bh);
-  return link_named_part(mainl, fd, idcode, name, params->flag);
+
+  ID *ret_id = nullptr;
+  if (!mainl->is_read_invalid) {
+    ret_id = link_named_part(mainl, fd, idcode, name, params->flag);
+  }
+
+  if (mainl->is_read_invalid) {
+    return nullptr;
+  }
+  return ret_id;
 }
 
 /* common routine to append/link something from a library */
@@ -4562,6 +4644,10 @@ static void library_link_end(Main *mainl, FileData **fd, const int flag)
   mainvar = static_cast<Main *>((*fd)->mainlist->first);
   mainl = nullptr; /* blo_join_main free's mainl, can't use anymore */
 
+  if (mainvar->is_read_invalid) {
+    return;
+  }
+
   lib_link_all(*fd, mainvar);
   after_liblink_merged_bmain_process(mainvar);
 
@@ -4582,9 +4668,13 @@ static void library_link_end(Main *mainl, FileData **fd, const int flag)
      * or they will go again through do_versions - bad, very bad! */
     split_main_newid(mainvar, main_newid);
 
-    do_versions_after_linking(main_newid, (*fd)->reports->reports);
+    do_versions_after_linking(*fd, main_newid);
 
     add_main_to_main(mainvar, main_newid);
+
+    if (mainvar->is_read_invalid) {
+      return;
+    }
   }
 
   blo_join_main((*fd)->mainlist);
@@ -4631,9 +4721,12 @@ static void library_link_end(Main *mainl, FileData **fd, const int flag)
 
 void BLO_library_link_end(Main *mainl, BlendHandle **bh, const LibraryLink_Params *params)
 {
-  FileData *fd = (FileData *)(*bh);
-  library_link_end(mainl, &fd, params->flag);
-  *bh = (BlendHandle *)fd;
+  FileData *fd = reinterpret_cast<FileData *>(*bh);
+
+  if (!mainl->is_read_invalid) {
+    library_link_end(mainl, &fd, params->flag);
+    *bh = reinterpret_cast<BlendHandle *>(fd);
+  }
 }
 
 void *BLO_library_read_struct(FileData *fd, BHead *bh, const char *blockname)
diff --git a/source/blender/blenloader/intern/readfile.h b/source/blender/blenloader/intern/readfile.h
index 027f1453581..c79dc0670d6 100644
--- a/source/blender/blenloader/intern/readfile.h
+++ b/source/blender/blenloader/intern/readfile.h
@@ -219,9 +219,9 @@ void blo_do_versions_cycles(struct FileData *fd, struct Library *lib, struct Mai
 void do_versions_after_linking_250(struct Main *bmain);
 void do_versions_after_linking_260(struct Main *bmain);
 void do_versions_after_linking_270(struct Main *bmain);
-void do_versions_after_linking_280(struct Main *bmain, struct ReportList *reports);
-void do_versions_after_linking_290(struct Main *bmain, struct ReportList *reports);
-void do_versions_after_linking_300(struct Main *bmain, struct ReportList *reports);
+void do_versions_after_linking_280(struct FileData *fd, struct Main *bmain);
+void do_versions_after_linking_290(struct FileData *fd, struct Main *bmain);
+void do_versions_after_linking_300(struct FileData *fd, struct Main *bmain);
 void do_versions_after_linking_cycles(struct Main *bmain);
 
 /**
@@ -232,6 +232,10 @@ void do_versions_after_linking_cycles(struct Main *bmain);
  */
 void *blo_read_get_new_globaldata_address(struct FileData *fd, const void *adr);
 
+/* Mark the Main data as invalid (.blend file reading should be aborted ASAP, and the already read
+ * data should be discarded). Also add an error report to `fd` including given `message`. */
+void blo_readfile_invalidate(struct FileData *fd, struct Main *bmain, const char *message);
+
 #ifdef __cplusplus
 }
 #endif
diff --git a/source/blender/blenloader/intern/versioning_280.c b/source/blender/blenloader/intern/versioning_280.c
index ff860677663..df2d6cd7d2b 100644
--- a/source/blender/blenloader/intern/versioning_280.c
+++ b/source/blender/blenloader/intern/versioning_280.c
@@ -1171,7 +1171,7 @@ static void do_version_fcurve_hide_viewport_fix(struct ID *UNUSED(id),
   fcu->rna_path = BLI_strdupn("hide_viewport", 13);
 }
 
-void do_versions_after_linking_280(Main *bmain, ReportList *UNUSED(reports))
+void do_versions_after_linking_280(FileData *UNUSED(fd), Main *bmain)
 {
   bool use_collection_compat_28 = true;
 
diff --git a/source/blender/blenloader/intern/versioning_290.cc b/source/blender/blenloader/intern/versioning_290.cc
index 580a1437c16..af78c38b577 100644
--- a/source/blender/blenloader/intern/versioning_290.cc
+++ b/source/blender/blenloader/intern/versioning_290.cc
@@ -410,7 +410,7 @@ static void version_node_socket_duplicate(bNodeTree *ntree,
   }
 }
 
-void do_versions_after_linking_290(Main *bmain, ReportList * /*reports*/)
+void do_versions_after_linking_290(FileData * /*fd*/, Main *bmain)
 {
   if (!MAIN_VERSION_ATLEAST(bmain, 290, 1)) {
     /* Patch old grease pencil modifiers material filter. */
diff --git a/source/blender/blenloader/intern/versioning_300.cc b/source/blender/blenloader/intern/versioning_300.cc
index 59e4be70989..1e4a3b51bea 100644
--- a/source/blender/blenloader/intern/versioning_300.cc
+++ b/source/blender/blenloader/intern/versioning_300.cc
@@ -939,7 +939,7 @@ static void version_geometry_nodes_primitive_uv_maps(bNodeTree &ntree)
   }
 }
 
-void do_versions_after_linking_300(Main *bmain, ReportList * /*reports*/)
+void do_versions_after_linking_300(FileData * /*fd*/, Main *bmain)
 {
   if (MAIN_VERSION_ATLEAST(bmain, 300, 0) && !MAIN_VERSION_ATLEAST(bmain, 300, 1)) {
     /* Set zero user text objects to have a fake user. */