The current building standards do not fully satisfy the fortification target required by the existing aseismic regulations. As building design continues to develop, more designers have adopted the performance-based seismic design approach. The costeffectiveness index is a crucial principle in this approach. In this study, an immune genetic algorithm is utilized to optimize the isolated structure based on the cost-effectiveness index by considering the characteristics of isolated structures. The seismic isolation design simultaneously considers the initial cost, cost of loss, and maintenance cost of the structure, and an integrated optimization of the isolated structure is conducted. An actual isolated building is used to obtain the optimal layout of the seismic isolation layer. The results demonstrate that isolated buildings are better equipped to ensure the security of the building and reduce economic loss throughout its lifetime.