To optimize injection molding process, the gating system, cooling systems and related injection molding process parameters are chosen as the experimental analysis factors, the quality of the injection as the experimental index in this paper. First, design the test program with orthogonal experimental and simulate with Moldflow MPI 6.0. Second, after plastic molding, in order to determine the integrated target, the comprehensive evaluation method of fuzzy mathematic is used to evaluate warpage values, shrinkage and residual stress. Finally, get the optimization scheme and the best match of gating system and cooling systems though the range and variance analysis of integrated target. The experimental results shown this optimization method can achieved the best parameters for practical produce. So, the optimization injection molding method, MPI and experimental design based, has important practical significance.