As　vital　raw　materials　in　the　chemical　industry,　2-methylfuran　(MeF)　and　2,5-dimethylfuran　(DMeF)　are　commonly　produced　as　mixtures.　The　selective　separation　of　MeF　and　DMeF　is　crucial　yet　challenging,　with　significant　industrial　and　economic　implications.　This　study　presents　an　energy-efficient　separation　technique　using　a　robust　calix[4]resorcinarene-based　supramolecular　porous　organic　cage　(POC),　CPOC-301,　to　effectively　capture　DMeF　from　an　equimolar　MeF/DMeF　mixture　within　2　h,　yielding　95.3%　purity.　The　exceptional　separation　efficiency　stems　from　the　superior　structural　stability　of　CPOC-301,　maintaining　its　initial　porous　crystalline　structure　during　separation.　Calculations　show　that　CPOC-301　forms　more　C-H···π　hydrogen　bonds　with　DMeF　versus　MeF,　accounting　for　its　DMeF　selectivity.　CPOC-301　can　be　easily　regenerated　via　heat　under　a　vacuum　and　reused　for　over　five　adsorption-desorption　cycles　without　significant　performance　loss.　This　work　introduces　an　approach　to　separate　similar　organic　molecules　effectively　using　POC　materials.　©　2024　The　Authors.　Co-published　by　Zhejiang　University　and　American　Chemical　Society.