Abstract: The seismic effect of pile-soil interaction on deep-water bridges with pile foundation is significant, and it is important for seismic design of these bridges to consider the effect of pile-soil interaction. A numerical simulation method for seismic response of bridge piers is proposed considering both the hydrodynamic pressure by additional mass method and the pile-soil interaction by a fine model, in which the initial ground stress is introduced by dynamic relaxation method. The proposed simulation method is verified through a centrifuge shaking table test. Then, the influence of seismic intensities and soil strengths on the seismic response of a deep-water bridge pier is analyzed. The results show that the pier displacement decreases as the soil strength increases, and the rule is not affected by the existence of water bodies. The hydrodynamic pressure has a small effect (less than 10%) on the seismic responses of the pier and the pile in soft foundation. The seismic responses of the pier and the pile in hard foundation increase significantly with the hydrodynamic pressure considered, and the amplitude increases with the seismic intensity. Therefore, the effect of hydrodynamic pressure on deep-water bridge structures in hard foundation under strong earthquakes must be taken into consideration in seismic design of bridge structures.