diff --git a/src/coreclr/jit/importer.cpp b/src/coreclr/jit/importer.cpp
index e745bce1bd037..3126025c0d922 100644
--- a/src/coreclr/jit/importer.cpp
+++ b/src/coreclr/jit/importer.cpp
@@ -2911,6 +2911,23 @@ int Compiler::impBoxPatternMatch(CORINFO_RESOLVED_TOKEN* pResolvedToken,
         case CEE_ISINST:
             if (codeAddr + 1 + sizeof(mdToken) + 1 <= codeEndp)
             {
+                // First, let's see if we can fold BOX+ISINST to just null if ISINST is known to return null
+                // for the given argument. Don't make inline observations for this case.
+                if ((opts == BoxPatterns::None) && ((impStackTop().val->gtFlags & GTF_SIDE_EFFECT) == 0) &&
+                    (info.compCompHnd->getBoxHelper(pResolvedToken->hClass) == CORINFO_HELP_BOX))
+                {
+                    CORINFO_RESOLVED_TOKEN isInstTok;
+                    impResolveToken(codeAddr + 1, &isInstTok, CORINFO_TOKENKIND_Casting);
+                    if (info.compCompHnd->compareTypesForCast(pResolvedToken->hClass, isInstTok.hClass) ==
+                        TypeCompareState::MustNot)
+                    {
+                        JITDUMP("\n Importing BOX; ISINST; as null\n");
+                        impPopStack();
+                        impPushOnStack(gtNewNull(), typeInfo(TYP_REF));
+                        return 1 + sizeof(mdToken);
+                    }
+                }
+
                 const BYTE* nextCodeAddr = codeAddr + 1 + sizeof(mdToken);
 
                 switch (nextCodeAddr[0])