diff --git a/pkg/dart2wasm/lib/target.dart b/pkg/dart2wasm/lib/target.dart
index 87e30c4b7d0..ff37a62a8bf 100644
--- a/pkg/dart2wasm/lib/target.dart
+++ b/pkg/dart2wasm/lib/target.dart
@@ -521,6 +521,13 @@ class WasmTarget extends Target {
         coreTypes.index.getClass('dart:_string', 'OneByteString');
   }
 
+  // In dart2wasm we can't assume that `x == "hello"` means `x`'s class is
+  // `concreteStringLiteralClass("hello")`, it may also be `JSStringImpl` when
+  // it's obtained from a JS call, or `TwoByteString` when it's a substring of a
+  // `TwoByteString`.
+  @override
+  bool get canInferStringClassAfterEqualityComparison => false;
+
   @override
   Class concreteClosureClass(CoreTypes coreTypes) {
     return _closure ??= coreTypes.index.getClass('dart:core', '_Closure');
diff --git a/pkg/kernel/lib/target/targets.dart b/pkg/kernel/lib/target/targets.dart
index fda4156a957..dcdda51e318 100644
--- a/pkg/kernel/lib/target/targets.dart
+++ b/pkg/kernel/lib/target/targets.dart
@@ -508,6 +508,10 @@ abstract class Target {
   Class? concreteDoubleLiteralClass(CoreTypes coreTypes, double value) => null;
   Class? concreteStringLiteralClass(CoreTypes coreTypes, String value) => null;
 
+  /// When a comparison `x == <literal>` is true, whether we can assume the
+  /// class of `x` to be `concreteStringLiteralClass(<literal>)`.
+  bool get canInferStringClassAfterEqualityComparison => true;
+
   Class? concreteAsyncResultClass(CoreTypes coreTypes) => null;
   Class? concreteSyncStarResultClass(CoreTypes coreTypes) => null;
 
diff --git a/pkg/vm/lib/transformations/type_flow/summary_collector.dart b/pkg/vm/lib/transformations/type_flow/summary_collector.dart
index 19bdfccefc5..87cfc9f1afa 100644
--- a/pkg/vm/lib/transformations/type_flow/summary_collector.dart
+++ b/pkg/vm/lib/transformations/type_flow/summary_collector.dart
@@ -1582,6 +1582,7 @@ class SummaryCollector extends RecursiveResultVisitor<TypeExpr?> {
               _isSubtype(lhs.variable.type,
                   _environment.coreTypes.intNullableRawType)) ||
           (rhs is StringLiteral &&
+              target.canInferStringClassAfterEqualityComparison &&
               _isSubtype(lhs.variable.type,
                   _environment.coreTypes.stringNullableRawType)) ||
           (rhs is ConstantExpression &&
diff --git a/tests/web/wasm/issue_59901_test.dart b/tests/web/wasm/issue_59901_test.dart
new file mode 100644
index 00000000000..04b15dfd8ab
--- /dev/null
+++ b/tests/web/wasm/issue_59901_test.dart
@@ -0,0 +1,18 @@
+// Copyright (c) 2025, the Dart project authors.  Please see the AUTHORS file
+// for details. All rights reserved. Use of this source code is governed by a
+// BSD-style license that can be found in the LICENSE file.
+
+import 'dart:js_interop';
+
+import 'package:expect/expect.dart';
+
+void main() {
+  final List<int> codeUnits = [];
+  final jsString = "hello".toJS.toDart;
+  if (jsString == "hello") {
+    for (int i = 0; i < 5; i += 1) {
+      codeUnits.add(jsString.codeUnitAt(i));
+    }
+  }
+  Expect.listEquals(codeUnits, [104, 101, 108, 108, 111]);
+}