Reactive　oxygen　species　(ROS)　played　an　essential　role　in　regulating　various　physiological　functions　in　living　organisms　and　treatment　of　malignant　disease.　Herein,　a　new　type　of　PEGylated　carbon　nitride　nanosheet@copper-doped　polyaniline　(CNNS@CuPANI)　with　nano-heterostructure　and　dual-modal　catalytic　ROS　generation　performance　was　synthesized.　Formation　of　the　nano-heterostructure　promoted　separation　of　photo-induced　electron-hole　pairs,　and　doping　of　Cu2+　further　increased　electron-transfer　rate　greatly.　Besides,　antenna　effect　of　the　CuPANI　endowed　the　heterostructure　with　near-infrared　light　utilization　ability,　finally　inducing　concurrences　of　oxygen-independent　type　I　and　oxygen-dependent　type　II　photodynamic　therapy　simultaneously.　Interestingly,　unleashing　of　doped　Cu2+　ions　responded　to　reductive　glutathione　in　tumor　microenvironment　further　triggered　a　Fenton-like　reaction,　and　such　PEGylated　CNNS@CuPANI　with　remarkable　ROS　generation　ability　was　therefore　employed　for　high-metastatic　orthotopic　osteosarcoma　therapy.　Cell　proteomics　analysis　illustrated　that　cell　survival　and　adhesion　were　considerably　altered　by　the　massively-generated　ROS,　which　also　affected　efficiencies　of　conspicuous　orthotopic　tumor　therapy　and　pulmonary　metastasis　resistance　in　vivo.　To　summarize,　our　newly-proposed　PEGylated　CNNS@CuPANI　achieved　desirable　effects　on　killing　orthotopic　osteosarcoma　and　preventing　metastasis,　providing　a　new　therapeutic　strategy　for　malignant　tumor　treatment.　©　2022　Elsevier　Ltd