A multi-region dynamic slip method was established to study the internal flow characteristics of the mixed-flow pump under the Alford effect. The ANSYS Fluent software and the standard k-ε two-equation model were used to numerically predict the mixed-flow pump’s external characteristics and analyze the forces on the impeller and guide vane internal vortex structure and non-uniform tip gap of the mixed-flow pump at different eccentric distances. The research results show that the external characteristic results of the numerical calculation are consistent with the experimental measurement. The head error of the design flow operating point is about 5%, and the efficiency error is no more than 3%, indicating the high accuracy of numerical calculation. Eccentricity has a significant influence on the flow field in the tip area of the mixed-flow pump impeller, the distribution of vortex core in the impeller presents obvious asymmetry, the strength and distribution area of the vortex core in the small gap area of the tip increase obviously, which aggravates the flow instability and increases the energy loss. With the increase of eccentricity, the strength and number of vortex core structures in the guide vane also increase significantly, and obvious flow separation occurs near the inlet of the guide vane suction surface on the eccentric side of the impeller. The circumferential distribution of L1 and L2 values represents the friction pressure gap in the eccentric state, and the eccentricity has a more noticeable effect on L1 and L2 values at the small gap; With the increase of eccentricity, the values of vorticity moment components L1 and L2 increase, and the Alford moment on the impeller increases. The leading-edge region of the blade is the main part affected by the unstable torque of the flow field. With the increase of eccentricity, the impact degree of tip leakage flow deepens, and the change of the tip surface pressure is the most obvious. The impact area of tip leakage flow is mainly concentrated in the first half of the impeller channel, which has an impact on the blade inlet flow field but has little impact on the blade outlet flow field.