In order to improve the traffic capacity of the expressway, ETC toll lane is gradually introduced into the toll station system. However, new traffic questions are also caused by the differences in the speed, passing time and other characteristics of ETC vehicles and traditional vehicles. On the basis of the analysis of the development trend of Expressway and toll station and the factors influencing the traffic safety of toll station, this paper makes qualitative analysis on the factors that affect the traffic safety of toll stations, and the reference factor of traffic conflict is established by introducing the number of lane changing and the average change of vehicle speed. On the basis of fully obtaining the information of Nanjing toll station of Nanjing Hangzhou expressway, the simulation software VISSIM is used to establish the simulation model, and on the basis of verifying correctness of the model, orthogonal test is used to analyse the factors that impact traffic safety of toll station, such as the number of ETC lane, the location of ETC toll lane, the proportion of ETC vehicles, total number of vehicles and etc. The traffic safety situation of toll stations under different schemes is determined.