Hydrofluorocarbons (HFCs) have important applications in different industries; however, they are environmentally unfriendly due to their high global warming potential (GWP). Hence, reclamation of used hydrofluorocarbons via energy-efficient adsorption-based separation will greatly contribute to reducing their impact on the environment. In particular, the separation of azeotropic refrigerants remains challenging, such as typical mixtures of CHsub.2Fsub.2 (HFC-23) and CHFsub.3 (HFC-32), due to a lack of adsorptive mechanisms. Metal–organic frameworks (MOFs) can provide a promising solution for the separation of CHFsub.3–CHsub.2Fsub.2 mixtures. In this study, the adsorption mechanism of CHFsub.3–CHsub.2Fsub.2 mixtures in TIFSIX-2-Cu-i was revealed at the microscopic level by combining static pure-component adsorption experiments, molecular simulations, and density-functional theory (DFT) calculations. The adsorption separation selectivity of CHsub.2Fsub.2/CHFsub.3 in TIFSIX-2-Cu-i is 3.17 at 3 bar under 308 K. The existence of similar TiFsub.6 sup.2− binding sites for CHsub.2Fsub.2 or CHFsub.3 was revealed in TIFSIX-2-Cu-i. Interactions between the fluorine atom of the framework and the hydrogen atom of the guest molecule were found to be responsible for determining the high adsorption separation selectivity of CHsub.2Fsub.2/CHFsub.3. This exploration is important for the design of highly selective adsorbents for the separation of azeotropic refrigerants.