Cationic polymers have great potential for cancer therapy due to their unique interactions with cancer cells. However, their clinical application remains limited by their high toxicity. Here we show a cell membrane-targeting cationic polymer with antineoplastic activity (P) and a second near-infrared (NIR-II) fluorescent biodegradable polymer with photosensitizer Bodipy units and reactive oxygen species (ROS) responsive thioketal bonds (P). Subsequently, these two polymers can self-assemble into antineoplastic nanoparticles (denoted mt-NP) which could further accumulate at the tumor and destroy cell membranes through electrostatic interactions, resulting in cell membrane destabilization. Meanwhile, the photosensitizer Bodipy produces ROS to induce damage to cell membranes, proteins, and DNAs to kill cancer cells concertedly, finally resulting in cell membrane lysis and cancer cell death. This work highlights the use of near-infrared light to spatially and temporarily control cationic polymers for photodynamic therapy, photo-immunotherapy, and NIR-II fluorescence for bio-imaging.