Stimuli-triggered　release　and　alleviating　resistance　of　iridium(Ⅲ)-based　drugs　at　tumor　sites　re-mains　challengeable　for　clinical　hepatoma　therapy.Herein,a　doxorubicin@iridium-transferrin(DOX@Ir-TF)nanovesicle　was　synthesized　by　carboxylated-transferrin(TF)and　doxorubicin-loaded　amphiphilic　iridium-amino　with　quaternary　ammonium(QA)groups　and　disulfide　bonds.The　QA　groups　enhanced　photophysical　properties　and　broadened　production　capacity　of　photoinduced-reactive　oxygen　species(ROS),while　the　disulfide-bridged　bonds　regulated　oxidative　stress　levels　through　reacting　with　glu-tathione(GSH);simultaneously,modification　of　TF　improved　recognition　and　endocytosis　of　the　nanovesi-cle　for　tumor　cells.Based　on　in-vitro　results,a　controlled-release　behavior　of　DOX　upon　a　dual-responsiveness　of　GSH　and　near-infrared　ray(NIR)irradiation　was　presented,along　with　high-efficiency　generation　of　ROS.After　an　intravenous　injection,the　nanovesicle　was　targeted　at　tumor　sites,realizing　TF-navigated　photoacoustic　imaging　guidance　and　synergistic　chemotherapy-photodynamic　therapy　under　NIR/GSH　stimulations.Overall,newly-synthesized　DOX@Ir-TF　nanovesicle　provided　a　potential　in　subcuta-neous　hepatocellular　carcinoma　therapy　due　to　integrations　of　targeting　delivery,dual-stimuli　responsive　release,synergistic　therapy　strategy,and　real-time　monitoring.