The currently available photodynamic sensitizers usually lead to undesirable side effects, including dark toxicity from heavy-atom effect and nonspecific phototoxicity. To address these issues, we designed and prepared a smart photosensitizer from boron dipyrromethene (BODIPY), and the dark toxicity and phototoxicity were reduced via heavy-atom-free substitution and controllable photosensitization, respectively. Importantly, the photodynamic effect together with fluorescence imaging can be simultaneously switched on through the suppression of intramolecular charge transfer (ICT) and photoinduced electron-transfer (PeT) induced by cancer-related biothiol glutathione (GSH) in a buffer solution. Moreover, the sensitizer exhibits obvious fluorescence enhancement and selective phototoxicity towards cancer cells in a biological system upon irradiation. The present monochromatic photosensitizer, which combines fluorescence imaging and targeted PDT treatment within a single chromophore, possesses great potentials as a new activatable theranostic reagent in cancer therapy.