Abstract: To improve the operation safety and reliability of nuclear power plants and reduce human error,the design of operation fault diagnosis system based on the theory of expert system and human factor engineering is researched in this paper.Firstly,the demand of the system functions is analyzed,and the definition of the key security parameters and their classification method is brought up.The safety state supervisory function module is briefly designed in order to facilitate the operator to monitor the safety state of the nuclear power plant from macroscopic to detail.Secondly,to maximize the speed and accuracy of the reasoning process and keep in line with the operator’s way of thought and experience,the structure of the operation fault diagnosis expert system is designed,as well as its database and knowledge base,along with a new method of reasoning that combines the hierarchical reasoning method with forward and backward reasoning method.