Due to the lack of effective longitudinal constraint for center tower, structural stiffness of three-tower suspension bridge becomes less than that of two-tower suspension bridge, and therefore it becomes more susceptible to the seismic action. By taking a three-tower suspension bridge-the Taizhou Highway Bridge over the Yangtze River with two main spans of 1080 m as example, structural dynamic characteristics and seismic performance of the bridge is investigated, and the effects of cable's sag to span ratio, structural stiffness of the center tower, and longitudinal constraint of the girder on seismic response of the bridge are also investigated, and the favorable structural system is discussed with respect to seismic performance. The results show that structural response under lateral seismic action is more remarkable, especially for the side towers, and therefore more attentions should be paid to the lateral seismic performance and also the side towers. Large cable's sag, flexible center tower and the longitudinal elastic cable between the center tower and the girder are favorable to improve structural seismic performance of long-span three-tower suspension bridges.