Abstract: The autonomous operation of Chang' E-4 is researched, including the acquirement of requirements, design of operation strategy and realization of the autonomous operation. The autonomous operation of Chang' E-4 addresses the unknown risks and assures the reliability and accuracy of key equipment based on the autonomous diagnosis, reconfiguration and management, which have been verified during the successful on-orbit demostration. The significant experiment of Chang' E autonomous operation will provide reference for the design of autonomous operation mission in deep space in the future.