This study develops a self-amplifying ROS-responsive nanoplatform, ECPCP, for simultaneous cuproptosis and cancer immunotherapy. ECPCP is composed of cinnamaldehyde (CA) and polyethylene glycol (PEG)-based polymer (PCP) encapsulating elesclomol (ES) and Cu compound (EC). ECPCP significantly prolongs the systemic circulation of EC and enhances tumor accumulation. Upon cellular internalization, the PCP coating dissociates in high ROS conditions, releasing ES and Cu, which trigger cuproptosis. The Cu²⁺-stimulated Fenton-like reaction and CA-induced ROS production break the redox homeostasis, inducing immunogenic cell death (ICD) of tumor cells. The excessive ROS accelerates the dissociation of ECPCP, forming a positive feedback loop against tumor self-alleviation. ECPCP improves the dual antitumor mechanism of ES and provides a potential optimization for its clinical application. In vitro and in vivo studies demonstrate the enhanced antitumor efficacy and biosafety of ECPCP.This study develops a self-amplifying ROS-responsive nanoplatform, ECPCP, for simultaneous cuproptosis and cancer immunotherapy. ECPCP is composed of cinnamaldehyde (CA) and polyethylene glycol (PEG)-based polymer (PCP) encapsulating elesclomol (ES) and Cu compound (EC). ECPCP significantly prolongs the systemic circulation of EC and enhances tumor accumulation. Upon cellular internalization, the PCP coating dissociates in high ROS conditions, releasing ES and Cu, which trigger cuproptosis. The Cu²⁺-stimulated Fenton-like reaction and CA-induced ROS production break the redox homeostasis, inducing immunogenic cell death (ICD) of tumor cells. The excessive ROS accelerates the dissociation of ECPCP, forming a positive feedback loop against tumor self-alleviation. ECPCP improves the dual antitumor mechanism of ES and provides a potential optimization for its clinical application. In vitro and in vivo studies demonstrate the enhanced antitumor efficacy and biosafety of ECPCP.