In the seismic design of bridge structures， the influence of local site conditions at piers on the seismic response should be considered. The multi?support response spectrum method is a common method for seismic performance analysis of bridge struc? tures under spatial ground motion. For deep?water bridge， the existing method cannot include the water?structure interaction. Based on the radiation wave theory， this paper proposed a multi?support response spectrum considering the water?structure interac? tion by introducing the term of hydrodynamic pressure into the vibration equation of the bridge. The correctness of the method was verified. Taking a typical five?span continuous girder bridge as an example， the seismic response of the bridge under different site conditions is studied by changing the site type of the pier， seismic intensity， and design seismic group. The influence law of local site effect on the seismic response of the multi?span continuous girder bridge is revealed. The results show that with the softening of site of pier 3， the relative displacement at top of pier 3 decreases by up to 93.0% at most. The influence of site type on pier displace? ment is greater than that of the axial force of girder and the bending moment at bottom of pier. With the increase of seismic intensi? ty， the relative displacement at top of pier， axial force of girder and bending moment at bottom of pier increase by 7 times. With the increase of epicenter distance， the relative displacement at top of pier increases by 41.0%， the axial force of girder increases approx? imately by 18.0%， and the bending moment at bottom of pier increases approximately by 30.0%.