Developing efficient adsorbent materials is crucial for adsorption and separation to realize the purification of energy source and raw chemicals. Here, we report a novel and robust 3D In‐based MOF built up with fluorine‐functionalized ligands, QMOF‐2F, with improved separation properties of C2‐light hydrocarbons over methane at room temperature respect isoreticular non‐fluorinated MOF. QMOF‐2F shows a remarkable chemical stability in different solvents, including water, and pH (2–12). DFT calculations support the key role of fluorine‐functionalization on the improved performance of QMOF‐2F.