A hybrid mid-story seismic isolation system with a smart damper has been proposed to mitigate seismic responses of tall buildings. Based on previous research, a hybrid mid-story seismic isolation system can provide effective control performance for reduction of seismic responses of tall buildings. Structural design of the hybrid mid-story seismic isolation system is generally performed after completion of structural design of a building structure. This design concept is called as an iterative design which is a general design process for structures and control devices. In the iterative design process, optimal design solution for the structure and control system is changed at each design stage. To solve this problem, the integrated optimal design method for the hybrid mid-story seismic isolation system and building structure was proposed in this study. An existing building with mid-story isolation system, i.e. Shiodome Sumitomo Building, was selected as an example structure for more realistic study. The hybrid mid-story isolation system in this study was composed of MR (magnetorheological) dampers. The stiffnessess and damping coefficients of the example building, maximum capacity of MR damper, and stiffness of isolation bearing were simultaneously optimized. Multi-objective genetic optimization method was employed for the simultaneous optimization of the example structure and the mid-story seismic isolation system. The optimization results show that the simultaneous optimization method can provide better control performance than the passive mid-story isolation system with reduction of structural materials.