A seismic response analysis of a piled raft foundation combined with cement deep mixing walls (DMWs), supporting a 12-story base-isolated building under strong earthquakes, was conducted using a three-dimensional finite element model. To evaluate the induced internal stresses in the DMWs against their capacity, a nonlinear elastic model with tensile and shear criteria was applied for the stabilized soil. In order to verify the deformation parameters of the DMWs and the soil, a numerical simulation was carried out using the moderate earthquake motion recorded during the 2011 Tohoku Earthquake. As the strong earthquake motion, Level 2 earthquakes with a mean return period of approximately 500 years were generated using two sets of phase data. Four numerical cases were conducted considering the effects of the presence of the DMWs on the seismic response of the piled raft system. Based on the dynamic analysis results, it is seen that the bending moments near the pile head were decreased significantly by the DMWs. This occurred because the amplification of the lateral ground displacements below the raft was restrained by the DMWs, and the shear force acting at the pile head was very small because the lateral external force acting at the bottom of the raft was carried mostly by the DMWs. It is also seen that the amplification of the acceleration response spectra of the raft with DMWs was substantially lower than that of the raft without DMWs in long periods of 1–2 s. This is probably due to the difference in the kinematic interaction effects between the foundation and the soft soil. Tensile and shear failure occurred in the DMWs, and the extent of the tensile failure was dominant. Nevertheless, it was found that the grid-form DMWs were quite effective for reducing the sectional force of the piles to an acceptable level, even if such partial failure occurred. The DMWs could be designed more rationally by following the principles of a performance-based design (PBD), because minor damage to DMWs can be tolerated under strong earthquakes provided that the required foundation performance has been satisfied.