Due to the frequent changes of external operating conditions, the mixed-flow pump usually operates under non-design conditions. Therefore, it is of great significance to carry out multi-condition optimization research to improve the mixed-flow pump operating efficiency.On the basis of verifying the accuracy of numerical simulation by experiment, an optimization system consisted of the circulation method, experiment design, response surface model and the optimization algorithm was used to optimization design the mixed-flow pump with a specific speed of 511, and the influence of each design parameters on each optimization objective was analyzed. The blade loading, blade trailing edge lean angle and spanwise distribution of impeller exit circulation were selected as design parameters, the pump efficiency at 0.8 times and 1.2 times of design flow were selected as optimization objectives, the pump head at design flow were selected constraint. The results showed that the spanwise distribution of impeller exit circulation had a great influence on the performance of the mixed-flow pump and should be carefully considered in the optimization design. The blade loading at hub should be fore-loaded, the blade loading at shroud should be aft-loaded, and the spanwise distribution of impeller exit circulation should increase gradually from hub to shroud to further improve the optimized mixed-flow pump efficiency. The pump efficiency of the optimized mixed-flow pump at 0.8 times, 1.0 times and 1.2 times of design flow were 81.11%, 88.38% and 80.56%, respectively. The pump head of the optimized mixed-flow pump at design flow was 12.33m, compared with that of the original model, these efficiencies were improved by 0.63 percentage points, 3.18 percentage points and 6.72 percentage points, respectively, the pump head fluctuation was also less than 2% at the same time. Therefore, the optimization method based on full circulation control was effective and can provide a reference for the same type of rotating machinery.