In plain English: x360ce is trying to protect its own files, but something in your PC is preventing it from saving or loading those files properly.
If you are trying to use (the popular Xbox 360 controller emulator) to make your non-standard gamepad work in modern PC games, you have likely encountered a frustrating roadblock. You set everything up, run the application as Administrator, and suddenly—a red error message appears: self protection failed error code 4 x360ce 2021
to allow the game's executable and x360ce to communicate without being blocked. Repair Online-Fix Files In plain English: x360ce is trying to protect
Technical Explanation (concise)