In order to simulate the energy efficiency fluctuation behavior of an industrial centrifugal pump with a six-blade impeller, a full-scale three-dimensional (3D) an unsteady state computational fluid dynamics (CFD) model was used. Five operational points with different flow fluxes were numerically investigated by using the Navier⁻Stokes code with shear-stress transport (SST) k-ω turbulence model. The predicted performance curves agreed well with the test data. A sine function was fitted to the transient calculation results and the results show that the efficiency fluctuates mainly on the blade passing frequency, while the fluctuation level varies with flow rate. Furthermore, high efficiency is not necessarily associated with low fluctuation level. The efficiency fluctuation level is high at part-load points, and becomes relatively low when flow rate exceeds the design value. The effect of change in torque is greater than that of the head lift with respect to fluctuations of efficiency. Based upon the analysis of velocity vector distribution of different impeller phase positions, a hypothesis which considers both the effect of pump’s structural shape and flow fluxes was proposed to explain the above behavior by analyzing the impeller⁻tongue interaction. This work enriches the theoretical system of flow parameters fluctuation of centrifugal pump, and provides useful insight for the optimal design of centrifugal pumps.