Petrochemical-related gases, especially light hydrocarbons with 1–8 carbon atoms, are essential industrial feedstocks. However, during steam cracking they inevitably coexist with other by-products in multi-component form. The huge amount of energy consumed by the traditional heat-driven distillation separation process encourages the development of energy-efficient adsorption separation technologies. Metal-organic frameworks (MOFs), which are porous sorbents with designable structures, have drawn considerable attention for use in molecular recognition and gas separation. In contrast to the widely studied use of MOFs for binary mixture separation, the separation of multi-component gases is closer to the practical situation in the hydrocarbon industry, but has higher requirements of the MOFs in terms of molecular recognition capability. However, there is a lack of discussion on the use of MOFs for multi-component separation from a structure–function relationship perspective. The present review comprises an extensive summary of current progress in the design of MOFs for multi-component hydrocarbon processes. Such processes include C2 hydrocarbon purification, C1-C4 gas mixture (except for the mixture containing C2 hydrocarbons only) separation, hexane/C8 isomeric hydrocarbon separation, and multi-component aromatic hydrocarbon separation. The different hydrocarbon selectivity capabilities of MOFs and the corresponding separation sequences in these separation scenarios are also highlighted. We appreciate the separation mechanism at a molecular level and emphasize the importance of MOF designability in achieving satisfactory separation performance. Furthermore, the challenges and perspective insights of multi-component gas separation using MOFs are discussed.