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I have the same problem in a multilingual site.

The problem is that the url called by ajax to save the node is rewrited in case of a multilingual site with the language prefix.
I suppose this is a problem only for multilingual sites with path prefix enabled, which is my case.

Here is a patch, that doesn't use url() drupal function to build the url that save the node :

      $settings['autosave']['url'] = '/autosave/handler/' . $token; // Don't use url('autosave/handler/' . $token) otherwise url is rewrited with the language prefix

My patch is for drupal 6 !
I've opened a new issue : #1847752: Doesn't save with language url prefix negotiation enabled