Vaned mixed-flow pump is widely used for liquid transportation in industry and agriculture. The structural-asymmetricity induces large axial force which causes axial vibration and shaft system damage. In this study, impeller forces are analyzed and optimized based on numerical simulation and experiment. Balance holes and a balance plate are used in cooperation. Orthogonal experiment is conducted to analyze the effects of balance hole diameter, sealing clearance width on the hub, and balance plate clearance width on axial force at design condition. Then, BP-artificial neural network is established with Global Dynamic Criterion algorithm. Efficiency and axial force at design condition are chosen as optimization objectives. The results prove that optimized pump has lower axial force and higher efficiency at design condition. The head coefficient meets design requirement. Accordingly, a cooperative method named the 'Combining Hole-Plate Pressure Balancing Method', made by adding balance holes and installing a balance plate in the hub clearance chamber, is proposed. The method can effectively reduce axial force and improve the adverse effect of axial force on the pump without obvious influence on hydraulic performance. This study is significant as a means to reduce axial force, lessen damage to a shaft system, and improve operation stability.