To evaluate the risk degree of relay protection equipment and find out the weak links of the relay protection system in time is of great importance to maintain the safe and stable operation of the power system. Taking the probability of failure and the degree of damage as the quantitative index of relay protection setting risk assessment, a method of protection setting risk assessment based on real-time information of secondary equipment on line is proposed. Based on the two aspects of rejection and misoperation of relay protection, the probability of incorrect operation of protection is calculated, and the hazard of incorrect operation of protection is quantitatively analyzed by the characteristic quantity of relative load loss. From the aspects of coordination relationship of relay protection setting and hardware defects of relay protection system, the online checking strategies of protection setting in the case of overall blocking and main blocking of protection device are studied, and a relay protection setting risk assessment model is established based on a single protection device. The method is proved to be reasonable and feasible through the constant value risk assessment of the line protection device in a certain area. The method is helpful to find the weak links of the relay protection system and to improve the safety and reliability of the power system. The research results have guiding significance to improve the safe and reliable operation of the power network. This work is supported by National Natural Science Foundation of China (No. 51307059) and Science and Technology Project of State Grid Southwest Branch (No. SGXN0000DDJS1800004).