Abstract: An eight-span simply-supported girder bridge of high-speed railway was taken as a research object, which crosses a strike-slip fault. By means of OpenSEES platform, an integrated non-linear model was established by considering bridge-track interaction. The fault-crossing horizontal ground motions were synthesized and inputted. The damage characteristics of bridge and CRTS II slab ballastless track structures were discussed under different earthquake intensities, and the seismic safety of structural components was evaluated quantitatively. With code control criteria of horizontal deformation, the running safety of track was assessed under different speeds, and the optimal design of track structure was discussed. The results show that the seismic responses of the fault-crossing span and its adjacent spans are the largest, and these bridge spans face great risk of damage. The horizontal deformation of track is obvious and the positions imposing potential threats to running safety are mainly the two ends of the fault-crossing span and its adjacent spans. By increasing the number of lateral rail block, the horizontal deformation of track can be effectively reduced. For the case of 6 pairs of rail block per span and line, the deformation can still meet the safety limit with speed of 100 km/h, except for the parallel turning angles of the fault-crossing span under rare earthquakes.