Based on the finite element program SAP2000, 120 models of eight different piers with different lead-rubber bearings (LRB) are established. The seismic response analyses of piers isolated by LRB in axial direction of the bridge are carried out under the excitations of seven earthquake waves. The calculations of seismic responses of the piers with and without isolation are implemented by using dynamic time-history analysis method, and the comparison of the results is given out. Considering the isolation ratio of the moment at the bottom of pier as observation samples, the variances of the three LRB mechanical parameters are analyzed. Furthermore, the ability of the parameters of LRB to adjust the seismic response of different piers is discussed. The analysis results show that all the mechanical parameters of LRB have significant effect on the isolation ratio of the moment at the bottom of pier, and the parameters of LRB can adjust the seismic forces of the isolated piers whose height difference is less than 30 meters to be almost equal. This paper provides some valuable references for the further study of isolation design for railway bridges.