Abstract: Seismic isolation structure system is an important means of disaster prevention and mitigation, which has developed rapidly in recent years. But its failure mechanism is different with other seismic structural system, and needs to be studied in combination with the superstructure and the isolation layer. The demand model and failure probability model of an isolated structure are established based on probabilistic safety assessment (PSA). According to the failure probability and the associated maximum damage probabilities of four failure modes of structure through vulnerability analysis, the weakest failure mode and optimized structure are found, so that the reliability of the isolated structure can be greatly improved. The demand function, failure probability function and maximum damage probability function are established based on a generic example and a practical engineering project, then the failure mechanism is studied, and the structure is optimized based on the presented theory, which shows the feasibility of the presented method.