In order to improve dynamic characteristics of a machining center column, this paper proposes a structural optimization method based on finite element method (FEM) and response surface method (RSM). In order to reduce number of design variables, the finite element analysis samples in design space are selected by using the central composite design (CCD) experiment method. On the basis of FEM results at these experiment samples, quadratic polynomials are employed to establish response surface model, which reflects the relationship between the response (mean frequency of the first four orders) and the design variables (the column structural sizes). The goal of getting maximum mean frequency is reached by using NLPQL algorithm in iSIGHT. Through the optimization, the mean frequency is increased by 8.12%.