In order to study the seismic performances of long-span cable-stayed bridge under two-stage horizontal fortification, relying on a long-span asymmetric cable-stayed bridge with high and low pylons, a spatial finite element model is established through the finite element model. The methods of response spectrum and linear time history comparative analysis are adopted. The analysis shows that the unfavorable sections of the main bridge under earthquake are the bottom sections of double pylons. Its low pylon is greatly affected by transverse seismic effect and the high pylon is greatly affected by longitudinal seismic effect. The reinforcement design should be optimized according to the stress direction.