The externally pre-stressed steel-box girder bridge is a novel structure, it has the advantage of lightness, less height and fast construction speed. The structure has a very bright application prospect in the future. Seismic effect of this kind of bridge was analyzed with the finite element method in combination of engineering practices. The dynamic characteristics, dynamic response under the action of E1 and E2 was calculated. The results of first five natural frequencies, mode of vibration, internal force and deflection under the action of seismic were listed and discussed. The results show that the externally pre-stressed steel-box girder bridge has a good seismic performance.