ZnPc-PEG2-VH032 is a light-degradable targeting chimeric compound (PDTAC) and cytotoxic agent that acts through the VHL pathway. It binds to the VHL ligand domain and induces specific VHL degradation under illumination, independent of nonspecific ROS-mediated protein damage. Using Zinc phthalocyanine as a photosensitizer, it generates ROS via Type I and II photodynamic pathways under 680 nm LED light, targeting and degrading bound VHL protein while exerting direct photodynamic cytotoxicity. VHL degradation subsequently reduces phosphorylation levels of CDK2/4, causing tumor cell cycle arrest and increasing tumor cells' sensitivity to ROS oxidative damage, achieving synergistic antitumor effects. ZnPc-PEG2-VH032 demonstrated significant in vivo efficacy in a non-muscle invasive bladder cancer (NMIBC) orthotopic mouse model.