Concerning that the residues of photosensitizers (PS) may cause serious side effects under light, it is of great significant to timely switch-off PS after photodynamic therapy (PDT). Herein, we proposed a supramolecular strategy to regulate the activity of PS, fabricating a supramolecular PS with improved reactive oxygen species (ROS) generation efficiency and accelerated self-degradation ability. During PDT treatment, the supramolecular PS exhibited good therapeutic efficiency as well as reduced dark toxicity. Moreover, the supramolecular PS could be degraded by ROS generated by itself and lose its PDT activities once PDT treatment finished. In this way, the side effects of PDT can be reduced without sacrificing the therapeutic efficiency. This work provides a novel strategy for smarter PDT beacon to further improve the safety of PDT treatment.