Using the conventional structural design methods, the design result is usually not the most economical and the most reasonable. While, using the single target structural optimization design method, duo to the only one target function to be optimized, the design result often can not meet with the multiple requirements of structural designing, furthermore its optimizing efficiency is low. So its application is limited. This paper proposes multi-target earthquake-resistant optimization design method for reinforced concrete frame structure under earthquake loading. In the optimization design approach, the ductility and cost which are two factors contradictory each other in structure designing are simultaneously taken as the target functions, and the function relation formula between them has been established, giving simultaneous consideration to the structural economy, safety and practicability. Using this design approach, the optimum cross-sectional dimensions, with the largest ductility and the lowest cost, of the reinforced concrete frame structure which is optimized under earthquake loading, can be obtained by computer. The practical examples of structure design, which have been optimized by using this approach, show that the cost of construction has been cut down by about 10% comparing with the conventional designing. The optimization process presented in this paper conforms entirely to the China national standards: “Code for Design of Reinforced Concrete Structures” (GB50010-2002) and “Code for Earthquake-resistant Design of Buildings” (GB50011). The theory and methods presented in this paper, having not only their theory meanings but their practical values, will be helpful for the structural design engineers and the researchers.