The bolt-flange structure is most one of joint mode, and stress and mass are its major performance parameters. The multi-object optimization of a bolt-flange structure can be performed by using Finite element method and optimization method unitedly. The response surface design method was employed to determine the combination of geometrical parameters to be designed of the bolt-flange structure. The stress of the bolt-flange structure which has the different geometrical parameters was numerically simulated and analyzed by using the software ANSYS. The response surface model is obtained. The optimized geometrical parameters of the bolt-flange structure were obtained by using MATLAB multi-objective optimization method. The results showed that the maximum equivalent stress in the optimized bolt-flange structure decreased 13.4% than that in the original one and the mass of the optimized bolt-flange structure was lower 14.3% than that of the original one.