The flame arrester sheet of explosion-proof valve with flame arrester was optimized to enhance its capability to reduce pressure and extinguish flame. Firstly, it introduced the principle of operation of explosion-proof valve with flame arrester. Secondly, the optimization object and variable were determined. Software FLUENT was adopted combining with homogeneous design method to carry out the numerical calculation. Then, regression analysis method was used to analyze the results and got the regression model of optimization objective. The results had shown that the regression model had its significance. Lastly, based on regression model of optimization objective, the solution of multi-objectives optimization was obtained applying linear weighting method. It is of importance to guide flame arrester structural design of explosion-proof valve.