diff --git a/clang-tools-extra/clang-tidy/utils/HeaderGuard.h b/clang-tools-extra/clang-tidy/utils/HeaderGuard.h
--- a/clang-tools-extra/clang-tidy/utils/HeaderGuard.h
+++ b/clang-tools-extra/clang-tidy/utils/HeaderGuard.h
@@ -38,6 +38,9 @@
   void registerPPCallbacks(const SourceManager &SM, Preprocessor *PP,
                            Preprocessor *ModuleExpanderPP) override;
 
+  /// Ensure that the provided header guard is a valid identifier.
+  static std::string sanitizeHeaderGuard(StringRef Guard);
+
   /// Returns ``true`` if the check should suggest inserting a trailing comment
   /// on the ``#endif`` of the header guard. It will use the same name as
   /// returned by ``HeaderGuardCheck::getHeaderGuard``.
diff --git a/clang-tools-extra/clang-tidy/utils/HeaderGuard.cpp b/clang-tools-extra/clang-tidy/utils/HeaderGuard.cpp
--- a/clang-tools-extra/clang-tidy/utils/HeaderGuard.cpp
+++ b/clang-tools-extra/clang-tidy/utils/HeaderGuard.cpp
@@ -24,6 +24,27 @@
   return std::string(Result.str());
 }
 
+/// Replace invalid characters in the identifier with '_'.
+static std::string replaceInvalidChars(StringRef Identifier) {
+  std::string Fixed{Identifier};
+  for (auto It = Fixed.begin(); It != Fixed.end(); ++It) {
+    // Identifier name must start with [A-z].
+    if (It == Fixed.begin() && isAsciiIdentifierStart(*It))
+      continue;
+    // The subsequent characters can be [A-z0-9].
+    if (It > Fixed.begin() && isAsciiIdentifierContinue(*It))
+      continue;
+    *It = '_';
+  }
+  return Fixed;
+}
+
+/// Remove all '_' characters at the beginning of the identifier. Only reserved
+/// identifiers are allowed to start with these.
+static StringRef dropLeadingUnderscores(StringRef Identifier) {
+  return Identifier.drop_while([](char c) { return c == '_'; });
+}
+
 namespace {
 class HeaderGuardPPCallbacks : public PPCallbacks {
 public:
@@ -164,6 +185,7 @@
                                          StringRef CurHeaderGuard,
                                          std::vector<FixItHint> &FixIts) {
     std::string CPPVar = Check->getHeaderGuard(FileName, CurHeaderGuard);
+    CPPVar = HeaderGuardCheck::sanitizeHeaderGuard(CPPVar);
     std::string CPPVarUnder = CPPVar + '_';
 
     // Allow a trailing underscore iff we don't have to change the endif comment
@@ -216,6 +238,7 @@
         continue;
 
       std::string CPPVar = Check->getHeaderGuard(FileName);
+      CPPVar = HeaderGuardCheck::sanitizeHeaderGuard(CPPVar);
       std::string CPPVarUnder = CPPVar + '_'; // Allow a trailing underscore.
       // If there's a macro with a name that follows the header guard convention
       // but was not recognized by the preprocessor as a header guard there must
@@ -278,6 +301,11 @@
   PP->addPPCallbacks(std::make_unique<HeaderGuardPPCallbacks>(PP, this));
 }
 
+std::string HeaderGuardCheck::sanitizeHeaderGuard(StringRef Guard) {
+  std::string Sanitized = replaceInvalidChars(Guard);
+  return dropLeadingUnderscores(Sanitized).str();
+}
+
 bool HeaderGuardCheck::shouldSuggestEndifComment(StringRef FileName) {
   return utils::isFileExtension(FileName, HeaderFileExtensions);
 }
diff --git a/clang-tools-extra/unittests/clang-tidy/LLVMModuleTest.cpp b/clang-tools-extra/unittests/clang-tidy/LLVMModuleTest.cpp
--- a/clang-tools-extra/unittests/clang-tidy/LLVMModuleTest.cpp
+++ b/clang-tools-extra/unittests/clang-tidy/LLVMModuleTest.cpp
@@ -219,6 +219,25 @@
                 "", "/llvm-project/clang-tools-extra/clangd/foo.h",
                 StringRef("header is missing header guard")));
 
+  // Characters outside [A-z0-9] are replaced with "_".
+  EXPECT_EQ("#ifndef FOO_BAR_TE_T_A_B_C_H\n"
+            "#define FOO_BAR_TE_T_A_B_C_H\n"
+            "\n"
+            "\n"
+            "#endif\n",
+            runHeaderGuardCheck("", "include/foo-bar/te$t/a(b)c.h",
+                                StringRef("header is missing header guard")));
+
+  // Subtitution of characters should not result in a header guard starting
+  // with "_".
+  EXPECT_EQ("#ifndef BAR_H\n"
+            "#define BAR_H\n"
+            "\n"
+            "\n"
+            "#endif\n",
+            runHeaderGuardCheck("", "include/$bar.h",
+                                StringRef("header is missing header guard")));
+
 #ifdef WIN32
   // Check interaction with Windows-style path separators (\).
   EXPECT_EQ(