The finite element model of AP1000 nuclear island structure was built by ANSYS and Midas Gen software platform, and its three-dimensional seismic response was analyzed through nonlinear time history method. The seismic response and seismic isolation control of the nuclear island structure under safe shutdown earthquake is investigated. In addition, the isolation period, stiffness ratio and flexion weight ratio is selected as the control parameters of the seismic isolation layer, to analyze the seismic isolation layer and superstructure seismic response with different seismic isolation layer parameters. The results show that, the base seismic isolation can significantly reduce the seismic response of the nuclear island structure. The superstructure top horizontal acceleration and shear of seismic isolation layer remarkably decreases with the increasing of the isolation period. Besides, the effect of flexion weight ratio and stiffness ratio on the seismic response of isolated nuclear island structure declines with the increasing of the isolation period.