In the present sand control operation, only the non-uniformity coefficient and particle size characteristic value of formation sand are considered for the selection of slotted screen width, which will lead to a large gap in the sand control effect under different working conditions. In order to obtain a more accurate selection principle of slotted width, the CFD-DEM method and orthogonal test were used to study the influence of different factors on the sand control performance of screen. And the study determined the primary and secondary order of the factors affecting the performance index of screen, established the regression equation model of three performance indexes and comprehensive sand control performance whose reliability was also tested simultaneously, and obtained the selection method of the optimal solution of width. The results show: (1) The main factors influencing the flow performance index are slotted width, production pressure difference, sand sphericity and hardness; The main factors influencing the sand retaining performance index are slotted width, fluid viscosity, sand sphericity and hardness; The main factor influencing the anti-blocking performance index is fluid viscosity. (2) Through orthogonal test, the order of the effect of the five factors on the three performance indexes of screen is obtained, and the best combination scheme is determined. (3) When the operating conditions are such as described in the article and the formation sand non-uniformity coefficient is more than 2, the slotted width of 0.37mm can obtain better comprehensive sand control performance of screen. This study can provide reference for the prediction of sand control performance of oil and gas wells and the accuracy optimization of sand control medium under specific working conditions.