Abstract: With the rapid development of national industry and mining, slurry pump is widely applied in transportation of two-phase flow as a sort of practical and reliable fluid machinery. Due to that the medium of centrifugal slurry pumps transport is fluid-solid two-phase medium, there is great difference for internal flow field between centrifugal slurry pumps and clean water pumps. Therefore, the design of the former is more complex and its design theory and method are not perfect now. In terms of performance, the main criticisms are its working head lower than design head, low efficiency and severe wear. So, it is a kind of equipment whose performance should be promoted rapidly in modern safe and effective industrial production. Thus, the optimal design of centrifugal slurry pumps is very meaningful for improving its performance. A centrifugal slurry pump with a specific speed of 75 was chosen as the research object. With the commercial CFD (computational fluid dynamics) software Fluent, RNG k-ε turbulence model and Eulerian two-phase flow model were selected to calculate its internal flow. The efficiency and the high efficiency region of the centrifugal slurry pump were set as the optimization goal. Design Expert 8.0.5b was used to make Plackett-Burman screening experimental design to pick out 3 structural parameters from 12 structural parameters of model pump, which were slurry pump blade inlet angle, outlet angle and wrap angle, set as the optimization variables, because too many structural parameters may affect the high efficiency area and the highest efficiency of centrifugal slurry pump. The 37-level uniform experiment was finished and the training and testing samples of RBF neural network were established. RBF (radial basis function) neural network was used to fit the relationship between the variables and objectives, which could be applied in NSGA-Ⅱ algorithm to get the Pareto optimal solution. Aiming at the result of the optional Pareto solution set, the optimal efficiency individual and high efficiency region individual were selected to compare with the initial model that was not optimized: The difference of external characteristic curves, distribution of absolute pressure at middle section of impeller runner and volute runner, relative velocity vector of fluid and solid phase, distribution of turbulence kinetic energy, distribution of solid concentration of pressure blades, blades back, front shroud and back shroud at middle section of impeller runner were all compared between the 2 extreme value individuals and initial individual. According to the analysis results of the differences between the performance curves of the above 3 individuals, the obtained optimal efficiency blade inlet angle, outlet angle and wrap angle were 21.76°, 23.43°, and 145.56°, respectively, and the high efficiency region blade inlet angle, outlet angle and wrap angle were 19.38°, 22.68°, and 116.71°, respectively. The experiment proved that the efficiency of the optimal individual was improved by 3.81% and the high efficiency region individual was improved by 4.33% compared with the original individual. The optimization results show that this optimization method improves the hydraulic characteristics of the impeller and the performance of centrifugal slurry pump.