diff --git a/llvm/lib/Transforms/Scalar/GVN.cpp b/llvm/lib/Transforms/Scalar/GVN.cpp
--- a/llvm/lib/Transforms/Scalar/GVN.cpp
+++ b/llvm/lib/Transforms/Scalar/GVN.cpp
@@ -2171,6 +2171,9 @@
     bool Changed = false;
     if (!I->use_empty()) {
       I->replaceAllUsesWith(V);
+      // Simplification can cause a special instruction to become not special.
+      // For example, devirtualization to a willreturn function.
+      ICF->clear();
       Changed = true;
     }
     if (isInstructionTriviallyDead(I, TLI)) {
diff --git a/llvm/test/Transforms/GVN/simplify-icf-cache-invalidation.ll b/llvm/test/Transforms/GVN/simplify-icf-cache-invalidation.ll
new file mode 100644
--- /dev/null
+++ b/llvm/test/Transforms/GVN/simplify-icf-cache-invalidation.ll
@@ -0,0 +1,46 @@
+%struct.zot = type { i32 (...)** }
+%struct.wombat = type { i8* }
+%struct.baz = type { i8, i8* }
+
+@global = hidden unnamed_addr constant { [4 x i8*] } { [4 x i8*] [i8* null, i8* null, i8* undef, i8* bitcast (void (%struct.zot*, i1)* @quux to i8*)] }, align 8
+
+define hidden void @eggs(%struct.zot* %arg) unnamed_addr align 2 {
+bb:
+  %tmp = alloca %struct.wombat, align 8
+  %tmp1 = getelementptr %struct.zot, %struct.zot* %arg, i64 0, i32 0
+  store i32 (...)** bitcast (i8** getelementptr inbounds ({ [4 x i8*] }, { [4 x i8*] }* @global, i64 0, inrange i32 0, i64 2) to i32 (...)**), i32 (...)*** %tmp1, align 8, !invariant.group !0
+  br i1 undef, label %bb4, label %bb2
+
+bb2:                                              ; preds = %bb
+  %tmp3 = atomicrmw sub i32* undef, i32 undef acq_rel, align 4
+  br label %bb4
+
+bb4:                                              ; preds = %bb2, %bb
+  %tmp5 = load %struct.baz*, %struct.baz** null, align 8
+  %tmp6 = getelementptr inbounds %struct.baz, %struct.baz* %tmp5, i64 0, i32 1
+  br i1 undef, label %bb9, label %bb7
+
+bb7:                                              ; preds = %bb4
+  %tmp8 = tail call i8* undef()
+  br label %bb9
+
+bb9:                                              ; preds = %bb7, %bb4
+  %tmp10 = load %struct.baz*, %struct.baz** null, align 8
+  %tmp11 = getelementptr inbounds %struct.baz, %struct.baz* %tmp10, i64 0, i32 0
+  %tmp12 = bitcast %struct.zot* %arg to void (%struct.zot*, i1)***
+  %tmp13 = load void (%struct.zot*, i1)**, void (%struct.zot*, i1)*** %tmp12, align 8, !invariant.group !0
+  %tmp14 = getelementptr inbounds void (%struct.zot*, i1)*, void (%struct.zot*, i1)** %tmp13, i64 1
+  %tmp15 = load void (%struct.zot*, i1)*, void (%struct.zot*, i1)** %tmp14, align 8
+  tail call void %tmp15(%struct.zot* %arg, i1 undef)
+  %tmp16 = getelementptr inbounds %struct.wombat, %struct.wombat* %tmp, i64 0, i32 0
+  %tmp17 = load i8*, i8** %tmp16, align 8
+  %tmp18 = icmp eq i8* %tmp17, null
+  ret void
+}
+
+; Function Attrs: nounwind willreturn
+declare hidden void @quux(%struct.zot*, i1) unnamed_addr #0 align 2
+
+attributes #0 = { nounwind willreturn }
+
+!0 = !{}