A mixed-flow pumping system was selected as the study case based on CFD technologies. Two difference methodologies of flow field analysis and performance prediction were conducted. One method was that the system efficiency was the production of pump efficiency with passage efficiency obtained by separate numerical simulation of suction box and discharge passage without pump. The other one was based on the simulation of whole pumping system including the suction box, discharge passage and pump. The predicted results from the two different methodologies were compared with model system test results, which showed that the predicted errors were different. The error of pumping system efficiency was smaller when the numerical simulation of whole pumping system was adopted, while the error was much greater when the system efficiency was predicted by the production of passage efficiency with pump efficiency, approximately equal only near the best efficiency point. The larger errors in predicting pumping system efficiency for the first method were mainly caused by unreasonable theoretic foundation. Therefore, it is suggested that the suction box, discharge passage and pump should be taken as a whole in numerical simulation and performance prediction and the effect of pump should be considered in the optimal hydraulic design of suction box and discharge passage. 