Abstract: In study of the flow of an isotopic gas mixture in a rotating cylinder, the isotope approximation method is generally introduced to decouple the flow problem of the mixed gas and the component transport problem by considering the small molecular weight difference. However, the isotope approximation is no longer applicable to the flow of a mixed gas with large mass difference in a rotating cylinder, and the coupling of flow and component transport problem is a difficulty in numerical simulation. Taking the normalized mass numbers of 0.93 and 0.07 of a binary gas mixture as the gas under consideration, this paper discusses the calculation method of the physical property coefficients of the binary gas mixture with a large mass difference. The fluid dynamic equations are discretized by a finite difference method, and the coupled flow and component transport equations under strong disturbance are solved by a Newton method modified by a homotopic continuation. The distributions of the flow field and concentration field of the binary gas mixture in the rotating cylinder under total reflux condition are obtained by numerical simulation. The results show that the flow circulation of each component in the mixed gas is very different. The circulation of the heavy component is concentrated near the side wall of the cylinder while the circulation of the light component circulation is distributed throughout the whole computational domain. The binary gas mixture with large mass number difference in a rotating cylinder shows radial separation under strong driving circulation. The axial abundance gradient of the binary gas mixture is enhanced by the side wall temperature disturbance and mechanical drive.