A cable seismic isolation system was proposed for long span continuous girder bridges in deep water. A method was presented for obataining the ground motion acceleration of different excitation points which based on the recorded ground motion arrays itself considering the spatial variability at the same time. Compared with the conventional system and the feeble fixed system, the seismic isolation effectivity of cable seisimc isolation system was studied when the spatial variability of ground motions was considered, and the effect of earthquake induced hydrodynamic pressure on the seismic response of deep-water bridges was discussed. The results indicate that the deep-water continuous girder bridges with cable-sliding friction aseismic bearing have remarkable isolation performance, and this bearing is sensitive to the spatially varying earthquake ground motions including wave-passage, incoherence and site-response effect. The effect of hydrodynamic pressure on the seismic response of bridges in deep water is different, considering the spatial variability of ground motions relative to a uniform excitation, which is also changed with apparent wave velocity, incoherence coefficient, local site condition when wave-passage, incoherence and site-reponse effect are considered. Therefore, this can provide a certain criterion of reference for seismic design of long-span deep-water bridges.