Aimed to base-isolated building with large plane dimension, the change laws of seismic response for base-isolated building under spatial variable ground motions were researched. Firstly, the artificial spatial variable earthquake time histories were generated using spectral representation method based on code response spectrum. Then the 3-D FEM modal of one based-isolated building with large plane dimension was established and the seismic response of based-isolated building under spatially ground motion was studied by nonlinear time history analysis. The mitigation effects of based-isolated building with large plane dimension were compared each other at the cases of uniform excitation, non-uniform excitation considering only wave passage effect, non-uniform excitation considering both the wave passage effect and incoherence effect, multi-component uniform excitation, multi-component non-uniform excitation considering the wave passage effect and multi-component non-uniform excitation considering both the wave passage effect and incoherence effect. The results show that the seismic response of base-isolated structure with large plane dimension under the uniform excitation is relative safety. When the base-isolated building with large plane dimension is designed by time history analysis, the spatial variability of earthquake ground motion effects can be considered.