diff --git a/packages/runtime-core/__tests__/components/KeepAlive.spec.ts b/packages/runtime-core/__tests__/components/KeepAlive.spec.ts
index 4dce5d144cf..08c9b94e6ca 100644
--- a/packages/runtime-core/__tests__/components/KeepAlive.spec.ts
+++ b/packages/runtime-core/__tests__/components/KeepAlive.spec.ts
@@ -874,4 +874,43 @@ describe('KeepAlive', () => {
     await nextTick()
     expect(serializeInner(root)).toBe('<p>1</p>')
   })
+
+  test('should correctly set ref with async component', async () => {
+    let resolve: (comp: Component) => void
+    const AsyncComp = defineAsyncComponent(
+      () =>
+        new Promise(r => {
+          resolve = r as any
+        })
+    )
+
+    const toggle = ref(true)
+    const instanceRef = ref<any>(null)
+    const App = {
+      render: () => {
+        return h(KeepAlive, () =>
+          toggle.value ? h(AsyncComp, { ref: instanceRef }) : null
+        )
+      }
+    }
+
+    render(h(App), root)
+
+    resolve!({
+      render() {
+        return h('div')
+      }
+    })
+
+    await timeout()
+    expect(instanceRef.value).not.toBe(null)
+
+    toggle.value = false
+    await nextTick()
+
+    toggle.value = true
+    await nextTick()
+
+    expect(instanceRef.value).not.toBe(null)
+  })
 })
diff --git a/packages/runtime-core/src/renderer.ts b/packages/runtime-core/src/renderer.ts
index 7cf8b49521f..ef4ecf027a4 100644
--- a/packages/runtime-core/src/renderer.ts
+++ b/packages/runtime-core/src/renderer.ts
@@ -477,7 +477,7 @@ function baseCreateRenderer(
 
     // set ref
     if (ref != null && parentComponent) {
-      setRef(ref, n1 && n1.ref, parentSuspense, n2 || n1, !n2)
+      setRef(ref, n1 && n1.ref, parentSuspense, n2 || n1, !n2, parentComponent)
     }
   }
 
@@ -2355,7 +2355,8 @@ export function setRef(
   oldRawRef: VNodeNormalizedRef | null,
   parentSuspense: SuspenseBoundary | null,
   vnode: VNode,
-  isUnmount = false
+  isUnmount = false,
+  parentComponent: ComponentInternalInstance | null = null
 ) {
   if (isArray(rawRef)) {
     rawRef.forEach((r, i) =>
@@ -2370,7 +2371,15 @@ export function setRef(
     return
   }
 
-  if (isAsyncWrapper(vnode) && !isUnmount) {
+  if (
+    isAsyncWrapper(vnode) &&
+    !isUnmount &&
+    // #4999
+    // when async-component in keep-alive, it should set ref to async-component
+    // so actual vnode in async-component can access right ref, because the
+    // keep-alive cache the wrapper vnode
+    !(parentComponent && isKeepAlive(parentComponent.vnode))
+  ) {
     // when mounting async components, nothing needs to be done,
     // because the template ref is forwarded to inner component
     return