Photodynamic　therapy　(PDT)　holds　great　promise　for　treating　various　types　of　cancer.　However,　its　clinical　advancement　is　hindered　by　the　intrinsic　hypoxic　tumor　microenvironment,　which　reduces　PDT　efficacy,　and　safety　concerns　related　to　the　biological　specificity　of　photosensitizers.　Here　we　constructed　a　MnO2　nanosheet　based　DNA　tetrahedron-photosensitizer　(TMPyP4)　nanoplatform　(TPM),　which　integration　with　tumor　targeting　(aptamer),　gene　drugs　(DNAzyme)　and　photosensitizer　agents　for　enhanced　PDT.　Once　the　TPM　entered　cancer　cells　through　aptamer　targeting,　the　MnO2　nanosheet　reacts　with　endogenous　acidic　and　H2O2　to　generate　Mn2+　and　oxygen　(O2),　thereby　alleviating　the　tumor　hypoxic.　Subsequently,　TMPyP4　further　converts　the　generated　O2　into　singlet　oxygen　(1O2)　under　near-infrared　light,　enhancing　PDT　efficacy　both　in　vitro　and　in　vivo.　Specifically,　the　generated　Mn2+　activates　the　DNAzyme　and　accelerate　tumor　target　mRNA　cleavage,　resulting　in　effective　PDT-gene　synergistic　therapy　for　tumors.　This　work　offers　novel　perspectives　on　advancing　precise　and　highly　effective　gene-PDT　systems.　©　2025　Elsevier　B.V.