An L-arginine-functionalized pillar[5]arene-based supramolecular photosensitizer LAP5⊃NBSPD was constructed by host-guest interactions, which could self-assemble into nano-micelles to achieve effective delivery and selective release of LAP5 and NBS in cancer cells. In vitro studies revealed that LAP5⊃NBSPD NPs exhibited excellent cancer cell membrane disruption and ROS generation properties, which provides a novel route for synergistically enhanced cancer therapeutic effectiveness.