In order to study the internal flow fields of mixed-flow pump with eccentric impeller, the numerical simulation and experiment have been conducted based on the dynamic sliding multi-region method. During simulation, the impeller domain has been separated by three sub-domains to apply the whirl effect. The pressure, turbulent kinetic dissipation and streamline distribution in the tip clearance were analyzed. The results show that the energy performance of calculation is basically consistent with the experimental results, which indicates the accuracy of energy performance prediction. The efficiency and head at the design flow condition drop about 20% and 11%, respectively, when e = 0.5 mm. The circumferential pressure distribution of impeller inlet and outlet is influenced greatly by the eccentric impeller, but the middle part of impeller suffered little effects as a result of the rotation effect of impeller. When the impeller is eccentric, the tip leakage flow and tip leakage vortex (TLV) are restrained at small tip clearance but enhance at large tip clearance. The angle between the TLV core and blade rim also increases at large tip clearance but decreases at small tip clearance. More energy has dissipated in the first half part of impeller channel within tip region, and the impacting depth increases with the increase in eccentricity, which affect the inlet flow fields of impeller at large eccentricity. The turbulent kinetic dissipation and hydraulic losses increase with the increase in eccentricity, which is the main factor for the decrease in pump efficiency.