Abstract: In order to study the influence of pile scour on the seismic response of offshore long-span cable-stayed Bridges, the three-dimensional models of the whole bridge are derived under different scouring depths by calculating the maximum scouring depth of the background engineering according to the existing classical theory and the stiffness of pile-soil interaction below the scouring line by "m" method, and effect of soil on pile foundation is equivalent to soil spring.Through dynamic analysis and seismic response time history analysis of the structure, the influence of different scouring depth of pile foundation on the seismic performance of long-span cable-stayed bridge was studied comparatively.The results show that the scouring makes the whole bridge structure more flexible and the natural vibration period longer; the greater the scouring depth, the greater the displacement response of pile foundation under earthquake; the influence of scouring depth on the shear force of pile foundation is related to the length of pile; the longer the pile foundation, the more complex the change trend of shear force; the adverse impact of scouring on the bridge increases with the increase of vibration intensity; the local scour of pile foundation will further aggravate the risk of bridge under earthquake action, and the scour problem should be paid attention to in seismic design.