As the number of high-rise buildings increases, a mid-story isolation system has been proposed for high-rise buildings. Due to structural problems, an appropriate isolation layer displacement is required for an isolation system. In this study, the mid-story isolation system was designed and the seismic response of the structure was investigated by varying the yield strength and the horizontal stiffness of the seismic isolation system. To do this, a model with an isolation layer at the bottom of 15th floor of a 20-story building was used as an example structure. Kobe(1995) and Nihonkai-Chubu(1983) earthquake are used as earthquake excitations. The yield strength and the horizontal stiffness of the seismic isolation system were varied to determine the seismic displacement and the story drift ratio of the structure. Based on the analytical results, as the yield strength and horizontal stiffness increase, the displacement of the isolation layer decreases. The story drift ratio decreases and then increases. The displacement of the isolation layer and the story drift ratio are inversely proportional. Increasing the displacement of the isolation layer to reduce the story drift ratio can cause the structure to become unstable. Therefore, an engineer should choose the appropriate yield strength and horizontal stiffness in consideration of the safety and efficiency of the structure when a mid-story isolation system for a high-rise building is designed.