Abstract: The technology of membrane separation has been widely used for producing high purity gas. Due to the limited capacity of a single membrane separator, a cascade is needed. According to the isotope separation theory and experimental results, a calculation model for the membrane-separator cascade was established, and the numerical simulation of cascade parameters was performed. The simulation results show that the required component in the purified product is able to reach up to a purity of 99.999% and is found little in the withdrawal of the impurity-end. Increasing the withdrawal of the impurity-end can enhance the purification effects of impurities with a heavier molar mass to improve the product’s quality. Membrane-separator cascade can be applied to improve gas’s purity as long as the molar mass of the required component is different from those of impurities. Therefore, using membrane-separator cascade is a practical method to produce high purity gas, which is technically simple and has good purifying performance and high recovery rate of the required component.