diff --git a/packages/vite/src/node/server/middlewares/transform.ts b/packages/vite/src/node/server/middlewares/transform.ts
index 17dd30cd2679fc..fd96921d8ea564 100644
--- a/packages/vite/src/node/server/middlewares/transform.ts
+++ b/packages/vite/src/node/server/middlewares/transform.ts
@@ -56,10 +56,25 @@ export function transformMiddleware(
       return
     }
 
-    let url = decodeURI(removeTimestampQuery(req.url!)).replace(
-      NULL_BYTE_PLACEHOLDER,
-      '\0'
-    )
+    let url
+    try {
+      url = decodeURI(removeTimestampQuery(req.url!)).replace(
+        NULL_BYTE_PLACEHOLDER,
+        '\0'
+      )
+    } catch (err) {
+      // if it starts with %PUBLIC%, someone's migrating from something
+      // like create-react-app
+      let errorMessage
+      if (req.url?.startsWith('/%PUBLIC')) {
+        errorMessage = `index.html shouldn't include environment variables like %PUBLIC_URL%, see https://vitejs.dev/guide/#index-html-and-project-root for more information`
+      } else {
+        errorMessage = `Vite encountered a suspiciously malformed request ${req.url}`
+      }
+      next(new Error(errorMessage))
+      return
+    }
+
     const withoutQuery = cleanUrl(url)
 
     try {