Parameter optimization of a static micro-mixer with a cantilever beam was accomplished for maximizing mixing efficiency using a sequential approximate optimization method. The objective function and design variables were chosen as mixing index, and the length and the angle measured from the horizontal of the cantilever beam, respectively. The Optimization problem of the mixer was considered as a series of sub-problems. Approximation to solve the sub-problems was performed by response surface methodology. To verify the reliability and the accuracy of the approximated objective function, ANOVA table and variable selection method were implemented, respectively. It was verified that the sequential approximate optimization method worked very well, and the mixing efficiency was significantly improved compared with the initial design.