Non-invasive　therapies　such　as　photodynamic　therapy　(PDT)　and　chemodynamic　therapy　(CDT)　have　received　wide　attention　due　to　their　low　toxicity　and　side　effects,　but　their　efficacy　is　limited　by　the　tumor　microenvironment　(TME),　and　monotherapy　cannot　achieve　satisfactory　efficacy.　In　this　work,　a　multifunctional　nanoparticle　co-assembled　from　oleanolic　acid　(OA),　chlorin　e6　(Ce6)　and　hemin　was　developed.　The　as-constructed　nanoparticle　named　OCH　with　diameters　of　around　130　nm　possessed　good　biostability,　pH/GSH　dual-responsive　drug　release　properties,　and　remarkable　cellular　internalization　and　tumor　accumulation　capabilities.　OCH　exhibited　prominent　catalytic　activities　to　generate　•OH,　deplete　GSH,　and　produce　O2　to　overcome　the　hypoxia　TME,　thus　potentiating　the　photodynamic　and　chemodynamic　effect.　In　addition,　OCH　can　induce　the　occurrence　of　ferroptosis　in　both　ferroptosis-sensitive　and　ferroptosis-resistant　cancer　cells.　The　multi-pronged　effects　of　OCH　including　hypoxia　alleviation,　GSH　depletion,　ferroptosis　induction,　CDT　and　PDT　effects　jointly　facilitate　excellent　anticancer　effects　in　vitro　and　in　vivo.　Hence,　this　work　will　advance　the　development　of　safe　and　effective　clinically　transformable　nanomedicine　by　employing　clinically-applied　agents　to　form　drug　combinations　for　efficient　multi-pronged　combination　cancer　therapy.　©　2023