In this study, parameter optimization of micro-static mixer with a cantilever beam was accomplished for maximizing the mixing efficiency by using successive response surface approximations. Variables were chosen as the length of cantilever beam and the angle between horizontal and the cantilever beam. Sequential approximate optimization method was used to deal with both highly nonlinear and non-smooth characteristics of flow field in a micro-static mixer. Shape optimization problem of a micro-static mixer can be divided into a series of simple subproblems. Approximation to solve the subproblems was performed by response surface approximation, which does not require the sensitivity analysis. To verify the reliability of approximated objective function and the accuracy of it, ANOVA analysis and variables selection method were implemented, respectively. It was verified that successive response surface approximation worked very well and the mixing efficiency was improved very much comparing with the initial shape of a micro-static mixer.