Abstract: To investigate the seismic response of MSSS (multi-span simply supported) bridge of Qinghai-Tibet Railway in a permafrost zone, Proper 3D analytical models of a 10?2m box girder MSSS Bridge are presented. The group pile-soil interaction is represented by equivalent foundation springs while the pounding effect of adjacent vibration units at the expansion joints is simulated by spring-damper elements. This paper studies the effects of thawed soil thickness, wave passage and pounding on seismic behaviours of the MSSS Bridge. It found that the stiffness of equivalent springs decreases with thawed soil thickness increase, seismic damages such as unseating failure and pier overturning more easily occur under a strong seismic action. The pounding occurs when the relative distance exceeds the gap distance between adjacent vibration units, which depends on the velocity of seismic wave and travel distance. When the velocity is low, the pounding effect is obvious and influences the seismic response of a bridge significantly, which can induce unseating failure very easily. Moreover, a bridge abutment also plays an important role in seismic response of a bridge system. Therefore, damages which may occur in summer under low wave velocity should be emphasized in the seismic assessment for MSSS bridges in a permafrost zone.