In order to solve the problem of input ground motion of fault-crossing structure and reveal its seismic response law, based on the physical model of the fault and the equivalent pulse function, this paper constructs a matrix considering the spatial variation characteristics of ground motion. A hybrid simulation method of high and low frequency superposition is proposed to simulate the input ground motion on both sides of the fault. Firstly, based on the established bridge site fault model, the stochastic finite-fault method is used to generate high-frequency ground motion at the target location. Secondly, according to the characteristics of pulse effect and permanent displacement of ground motion on both sides of the strike-slip fault, different equivalent pulse models are used to simulate the parallel and normal low-frequency pulse components of the fault respectively. The Butterworth filter is used for high-pass and low-pass filtering at the cut-off frequency. According to the drilling data, site model and the spatial coherence of ground motion on both sides of the strike-slip fault, a transformation matrix is established to simulate its spatial variability. Finally, the high and low frequency components after matched filtering are superimposed in time domain to obtain the input ground motion on both sides of the fault. The rationality of results is examined in three aspects including time history, response spectrum and structural response. 3D dynamic finite-element model of the actual fault-crossing suspension bridge is established using OpenSees to analyze the seismic response under the simulated ground motions. The results show that the angle and position of the fault-crossing and the amplitude of the permanent displacement have a significant influence on the seismic response of the fault-crossing bridge. The large residual internal force and residual displacement are the important reasons for the damage of the bridge.