Abstract: A CFD model based on MicroChannel Distillation （MCD） was built to simulate the separation process of mixtures with low relative volatility. The heat and mass transfer process of propylene/propane two-phase mixture flow in MCD equipment was simulated by multi-physics coupling. The mass transfer coefficients of mixture at different temperatures and molar concentrations were simulated based on the Maxwell-Stephan diffusion model. The results show that the liquid propylene/propane mixture with cold-end 235 K and hot-end 239 K can be efficiently separated under the condition of 170 kPa with 3.8 mm MCD equipment, and the propane concentration of the product can be increased from 1% to 2.1%. The effects of flow field, temperature and structure on the heat and mass transfer efficiency of distillation were obtained. This research has important guidance for improving the efficiency of cryogenic MCD system.