A reliable and convenient optimism method was introduced. Based on a mixed-flow pump designed by 3-dimensional inverse design method and combined with CFD, an optimization design was conducted with the blade-loading as the design variable and the hydraulic efficiency as the optimization objective. With CFD simulation results, the relationship between the hydraulic efficiency and the blade-loading was established by orthogonal test and response surface method. The optimization results show that the blade loading on hub near leading edge has the most significant influence on the hydraulic efficiency. Compared with the pump model with the reference impeller, the hydraulic efficiency of the pump model with optimized impeller increases by 3.2% while the head keeps constant.