How to isolate the relevant secondary equipment safely and reliably from each other in the expansion, renovation, and maintenance of smart substation is a problem to be solved. This paper puts forward the method and principle of the safety isolation of the secondary equipment, which use the anti-misoperation system to solve the problem of security isolation of the secondary equipment. Firstly, this paper studies the information flow and anti-misoperation requirement of the secondary equipment security measures, and then proposes four function modules of the anti-misoperation system which includes security measures billing, setting anti-misoperation, security measures implementation, and security measures execution. After that, this paper expounds the key technology of the security measure, such as technical route, analysis principle, analysis criterion, etc. Application results show the feasibility of the introduced implementation scheme of the anti-misoperation system.