A evaluation of seismic resistance capacity of Double-Tower-Connected and Deck-Separated cable-stayed bridge with four cable-planes is presented by using methods of response spectrum analysis and time-history analysis. First of all, the dynamic characteristics are discussed under two different boundary conditions at the bottom of the bridge tower, i.e. the fixed end and the pile-soil interaction. Secondly, response spectrum analysis on the model with piles has been made in accordance with two kinds of probabilities of exceedance. Based on two kinds of mode combination methods and three groups of mode numbers, the maximum seismic response of the structure is discussed. And then, the time-history analysis has been carried out and the internal forces, displacement and the time history response of main-beams and pylons are obtained. The analytical results show that the seismic resistance capacity of the bridge can satisfy the requirement. The semi-floating system with the damping device system is appropriately designed for reducing the seismic response. It is suggested that the structural internal forces and deformations of long-span cable-stayed bridges should be analyzed by using the two methods and the maximum values from them should be used for the aseismatic design of bridges.