An optimization design method based on three-dimensional inverse design method and CFD was developed by combining design of experimental method, response surface method and simulated annealing optimization calculation. The shape parameters of meridional channel and blade were taken as optimization design parameters, and the impeller efficiency was setting as the optimization object. The shape parameters of the blade were expressed by velocity circulation distribution parameters through three-dimensional inverse design method. The optimization method was applied to a centrifugal fan impeller with the efficiency improved by 3.3%. The effects of the meridional channel shape parameters, circulation parameters and their interaction effects on the impeller efficiency were analyzed according to the constructed response surface between the design parameters and the impeller efficiency. It is shown that the lean angle of the blade leading edge on meridional channel played an important role on the impeller efficiency. Compared with the hub, the shape curve and the circulation distribution shape on the shroud have more influences on the efficiency.