The large-span bridges always employ high-pile foundations, and its seismic response will take an important responsibility to affect the dynamic characteristics of whole bridge. In order to understand the effect of pile-soil dynamic interaction on dynamic characteristics and plastic development of the whole cable-stayed bridge system, the elasto-plastic seismic response of an actual cable-stayed bridge engineering considering material nonlinear was analyzed. And for reflecting the effect of pile-soil interaction, there were two modals applying to calculation. The results show that after considering pile-soil interaction, the structural actual dynamic characteristics can be more accurately reflected; pile-soil interaction performs a great influence on bending moment and shearing force of main girder and tower and the development of plastic zone get decrease. Meanwhile, Seismic wave chosen can greatly affect the response of structure. It will provide a basis for ensuring the ductility of structure and improving the seismic performance of structure.