In order to analyze the effect of blade thickness of impeller on the energy performances and optimize the hydrodynamic performance in the mixed-flow reactor coolant pump (RCP), the 100 type mixed-flow RCP is taken as the research object. Three impellers with different blade thicknesses were designed by choosing the thickness of impeller blade as the optimization design variable. The numerical simulation and performance prediction of the original model are carried out firstly. By comparing with the experimental data of the original model, the reasonable numerical simulation method and the reliability of the performance prediction are determined. Through the whole passage's numerical calculation and analysis of three impellers with different blade thicknesses, the effect of different blade thicknesses on the external characteristics and internal flow field distribution of RCP is predicted and analyzed. The results showed that the head of RCP increases and the efficiency decreases with the decreasing of the thickness of impeller blade under the same flow condition. Because of the special structure of the space guide vane, the decreasing of the impeller blade thickness causes reflux phenomenon at the inlet of the guide vane, which increases the flow loss in the guide vane, and the pressure in the whole flow path is overall higher. Therefore, properly increasing the blade thickness is helpful to improve the efficiency of RCP with special spatial guide vane structure and ensure the reliability of the operation of RCP.