diff --git a/crates/oxc_minifier/src/peephole/normalize.rs b/crates/oxc_minifier/src/peephole/normalize.rs
index 70136b9c5bc0f..c64a9a32eefdf 100644
--- a/crates/oxc_minifier/src/peephole/normalize.rs
+++ b/crates/oxc_minifier/src/peephole/normalize.rs
@@ -243,18 +243,21 @@ impl<'a> Normalize {
         e.argument = ctx.ast.expression_numeric_literal(ident.span, 0.0, None, NumberBase::Decimal);
     }
 
-    fn set_no_side_effects(pure: &mut bool, callee: &Expression<'a>, ctx: &TraverseCtx<'a>) {
+    fn set_no_side_effects(
+        pure: &mut bool,
+        callee: &Expression<'a>,
+        ctx: &TraverseCtx<'a>,
+    ) -> Option<()> {
         if !*pure {
-            if let Some(ident) = callee.get_identifier_reference() {
-                if let Some(symbol_id) =
-                    ctx.scoping().get_reference(ident.reference_id()).symbol_id()
-                {
-                    if ctx.scoping().no_side_effects().contains(&symbol_id) {
-                        *pure = true;
-                    }
-                }
+            let ident = callee.get_identifier_reference()?;
+            // The `reference_id` may be `None`(e.g. after `ReplaceGlobalDefines` plugin) after previous passes.
+            let symbol_id = ctx.scoping().get_reference(ident.reference_id.get()?).symbol_id()?;
+
+            if ctx.scoping().no_side_effects().contains(&symbol_id) {
+                *pure = true;
             }
         }
+        Some(())
     }
 }
 
diff --git a/napi/transform/test/transform.test.ts b/napi/transform/test/transform.test.ts
index 0401df18572ce..620ef5da0c9bc 100644
--- a/napi/transform/test/transform.test.ts
+++ b/napi/transform/test/transform.test.ts
@@ -244,6 +244,26 @@ describe('define plugin', () => {
     });
     expect(ret.code).toEqual('console.log({ __TEST_DEFINE__: "replaced" });\n');
   });
+
+  it('should not panic when transform a local variable to a global variable', () => {
+    // https://github.com/rolldown/rolldown/issues/4261
+    const code = `function load(url, successCallback, errorCallback) {
+	var xhr = new XMLHttpRequest();
+	xhr.send(null);
+}`;
+    const ret = transform('test.ts', code, {
+      define: {
+        'XMLHttpRequest': 'undefined',
+      },
+    });
+    expect(ret.code).toEqual(
+      `function load(url, successCallback, errorCallback) {
+	var xhr = new undefined();
+	xhr.send(null);
+}
+`,
+    );
+  });
 });
 
 describe('inject plugin', () => {