Taking the multi-objective design of SRC frame-RC core wall hybrid structure as an example, minimizing the project cost and damage was taken as the optimization objective by introducing damage function. According to the three-level anti-seismic fortification criterion, as well as the mechanical characteristics of the structure, the three-level anti-seismic fortification criterion optimization design method was presented: the optimization of component section and concrete volume was actualized assuming that only the concrete works under minor earthquake; the optimization of steel volume was brought into effect for meeting the requirement of minimum displacement difference between two adjacent storey under moderate earthquake, in which the frame and shear wall are in collaborative working state; the optimization of steel volume was implemented farther for meeting the requirement of minimum structure damage under severe earthquake, in which the structure was in plastic state and the shear wall was out of work. This method transformed the multi-objective optimization problem into multiple single objective optimization problems. Taking the various constraints into consideration, the failure modes-based three-level anti-seismic optimal design of SRC frame-RC core wall hybrid structure were actualized by using the combination of the genetic algorithm with the optimization criterion, i.e. OC-GA algorithm. A numerical example of 24 stories SRC frame-RC core wall structure was analyzed to verify the rationality of the proposed method.