Mixed matrix membranes were made of polysulfone and Matrimid® polymers, and SiO2 and TiO2 nanoparticles in order to improve the efficiency of polymeric membrane in gas separation and review the efficiency of membrane separation process, laboratory. The modeling results of selectivity and permeability of gases O2, N2, CO2 and CH4 were discussed for different membranes. Another objective of this study was to submit a report on the importance of the statistical analysis and modeling in design and optimizing mixed matrix membranes to separate gas. The D-optimal method was applied to model and optimize the selectivity and permeability due to the main parameters. The obtained results indicated that the permeability of all gases demonstrated an ascending trend when the nanoparticles were increased. Under optimized conditions, the permeability of the gases O2, N2, CO2, CH4 in the membrane of PSF (12)/SiO2 (13.82) was 2.49, 1.113, 12.82 and 0.885 Barrer, respectively. A statistical method was practiced in the current research to design, optimize and separate gas membranes through effective efficiency for different applications.