Recently,　chiral　inorganic　nanomaterials　have　attracted　considerable　interest　for　their　chiroptical　property　and　chirality-dependent　phototherapeutic　performance.　Herein,　for　the　first　time,　we　propose　a　near-infrared　circularly　polarized　light　(NIR-CPL)　responsive　supramolecular　hydrogels　with　high　ground　state　chirality　(|gabs|　up　to　3.2　×　10−2)　and　intense　upconverted　circularly　polarized　luminescence　activity　(|glum|　up　to　2.6　×　10−2)　for　tumor　photodynamic　therapy.　After　supramolecular　co-assembly,　methylene　blue　loaded　lanthanide　upconversion　nanoparticles　(UCMBs)　are　effectively　attached　to　the　helical　nanofibers　constructed　by　amino　acid　precursors,　which　can　achieve　NIR-CPL　triggered　reactive　oxygen　species　(ROS)　production.　The　obtained　hybrid　hydrogels　exhibit　efficient　NIR　light　conversion,　improved　photodynamic　performance　and　efficient　tumor　inhibition.　These　findings　provide　a　new　perspective　for　exploring　NIR-CPL　responsive　upconversion　materials　with　outstanding　chirality-dependent　phototherapy　characteristic　and　efficient　therapeutic　outcomes　for　further　biomedical　application.　©　2023　Elsevier　B.V.