The central composite design of the response surface methodology is applied to optimize ge- ometrical parameters of a multistage pump impeller in this paper, and a relevant experiment was conducted. The maximum head difference is 5.6%, and the maximum efficiency differ- ence is 0.73%, which can ensure the accuracy of the investigation. Meanwhile, 30 groups of test schemes are obtained based on the software Design Expert, and the numerical calcula- tion of each scheme is conducted. According to the calculation results and variance analysis, it is found that the effect of response variables of the primary terms blade number, impeller outlet diameter, blade outlet width, and the quadratic terms between the blade number and impeller outlet diameter, blade number and blade wrap angle, impeller outlet diameter and blade outlet width on the head are significant. However, the primary term blade wrap an- gle, the quadratic terms between the blade number and blade outlet width, impeller outlet diameter and blade wrap angle, blade wrap angle and blade outlet width have no significant effect on the head. Furthermore, a response surface regression model of the single-stage im- peller head of a multistage pump was established after removing insignificant factors, and the deviation of the response surface regression model is only 2.4%. The significant sequence of the influence of response variables on the head is the blade number, impeller diameter, blade outlet width, and blade wrap angle. Finally, the optimal geometrical parameters of the impeller are obtained: the number of blades is 6, the diameter of the impeller is 254 mm, the blade wrap angle is 119◦, the outlet width of the blade is 4.3 mm, and the predicted value of the head is 189.19 m. Therefore, the influence rule of impeller geometrical parameters on the head was obtained, which can provide theoretical references for the optimization design of the multistage pump impeller.