Abstract: The Jia-min Elevated Route in Shanghai was taken as the research object. OpenSees was adopted to establish finite element models and nonlinear time-history analyses were carried out to compare the seismic response of the girder, pier column and foundation under two kinds of pile foundation systems for a regular continuous girder bridge. The influence of change of pier height was also considered. The results show that compared with the traditional foundation system, by using pile foundation that is allowed to uplift and increasing the pier height from 5 m to 20 m, the maximum bending moment of the pier is greatly reduced by 20.4%~32.0% under longitudinal earthquake input and by 2.5%~23.8% under transverse earthquake input. The maximum longitudinal bending moment of the single pile is also decreased by 16.2%~40.0%. The maximum tensile force of a single pile is controlled effectively. Based on the new two-level seismic fortification criterion, the seismic performance of the pier column and foundation under E2 earthquake was evaluated. The results show that by allowing foundation uplift in a regular girder bridge, the seismic demand of pier column and foundation can be greatly reduced. Under E2 earthquake, all the pier columns are kept in elastic states, and the reinforcement ratio in a single pile can be reduced with the increase of pier height, compared to that of bridges using conventional pile foundation.