The　separation　of　hydrogen　isotopes　under　moderate　conditions　remains　a　significant　challenge,　primarily　due　to　their　nearly　identical　physicochemical　properties.　Among　emerging　approaches,　the　chemical　affinity　quantum　sieving　(CAQS)　effect　in　porous　materials　has　shown　promise　for　achieving　selective　adsorption　at　elevated　temperatures.　Herein,　we　evaluate　the　isotope　separation　performance　of　MIL-101　(Cr),　a　hydrothermally　stable　metal-organic　framework　featuring　supertetrahedral　cages　and　open　metal　sites.　The　synergistic　interaction　between　these　structural　motifs　imparts　a　high　adsorption　enthalpy,　promoting　strong　isotope-framework　interactions.　In　combination　with　its　large　pore　size　and　high　porosity,　which　enhance　molecular　exchange,　MIL-101　(Cr)　exhibits　effective　hydrogen　isotope　separation,　as　confirmed　by　dynamic　breakthrough　experiments　conducted　up　to　100　K.