Abstract: To avoid global collapse of high-rise building structures caused by the damage of weak stories, a multi-objective optimization method based on damage control function of story group and failure probability was proposed. Through incremental dynamic analysis, the peak acceleration corresponding to the structural failure probability of 50% was selected as the objective earthquake intensity, and two performance indices:the damage control function of story group and failure probability, were defined and the section dimension of components was used as the variables to conduct the structural optimization analysis. A 30-story reinforced concrete frame-core structure was optimized, and the seismic performance of structure before and after optimization was assessed based on PACT (Performance Assessment Calculation Tool). Results indicate that the inter-story drift angle distribution of the optimized structure is more uniform than that of the original structure, and the damage is gradually decreased from the top to the bottom. The Collapse Margin Ratio (CMR) is increased by 29.8, and the repair cost is reduced for both the frame and core tube. The working coordination between the wall and the frame is strengthened, and the seismic perfomance of the structure after optimization has been significantly improved.