Nitric　oxide　(NO)　is　a　gaseous　signal　molecule　with　multiple　physiological　functions,　and　it　also　plays　a　key　role　in　cancer　therapy.　However,　the　production　of　NO　which　depends　on　O-2　or　H2O2　is　limited　within　the　tumor　microenvironment,　leading　to　unsatisfactory　anticancer　effect.　Herein,　we　report　a　NO-based　phototherapeutic　strategy　mediated　by　photogenerated　holes　for　hypoxic　tumors,　which　is　achieved　by　irradiation　of　the　poly-L-arginine　modified　carbon-dots-doped　graphitic　carbon　nitride　nanomaterial　(ArgCCN).　Upon　red　light　irradiation,　the　photogenerated　holes　on　ArgCCN　oxidized　water　into　H2O2　which　subsequently　oxidized　the　arginine　residues　to　produce　NO.　In　vitro　and　in　vivo　experiments　showed　that　the　high　concentration　of　NO　produced　by　ArgCCN　could　induce　cancer　cell　apoptosis.　The　presented　phototherapeutic　strategy　is　based　on　microenvironment-independent　photogenerated　holes　mediated　oxidation　reaction,　paving　the　way　for　the　development　of　NO　therapeutic　strategy.