In this paper, the Hong Kong-Zhuhai-Macao long-span continuous isolated bridge was studied. The fiber-plastic hinge element was used to simulate the nonlinear state of the reinforced concrete pier, and a 3D finite element model of the full bridge was established. The time history analysis of the isolated and non-isolated bridges were carried out. Seismic performance of the isolated and non-isolated bridges under the action of rare and extremely rare earthquakes was quantitatively evaluated by using the curvature ductility ratio of bridge pier and the ultimate allowable displacement of bearing as the indexes of bridge damage and failure. The failure modes of isolated and non-isolated bridges were discussed, and the influence of material nonlinearity on the seismic response of bridge structure was also studied. The results showed that, whether material nonlinearity is considered or not has a great impact on the seismic response of non-isolated bridge and a small impact on the isolated bridge. Under strong earthquakes, the seismic performance of isolated bridges was significantly higher than that of non-isolated bridges, and their failure mode are also different. The pier of isolated bridge is not damaged, for the pier components are well protected. The pier of non-isolated bridge is seriously damaged under extremely rare earthquake, and the pier components are damaged before the pot bearing.