Here,　we　have　synthesized　and　characterized　a　novel　activatable　photosensitizer　(PS)　8a　in　which　two　well-designed　boron　dipyrromethene　(BODIPY)　derivatives　are　utilized　as　the　photosensitizing　fluorophore　and　quencher　respectively,　which　are　connected　by　a　disulfide　linker　via　two　successive　Cu　(I)　catalyzed　click　reactions.　The　fluorescence　emission　and　singlet　oxygen　production　of　8a　are　suppressed　via　intramolecular　fluorescence　resonance　energy　transfer　(FRET)　from　the　excited　BODIPY-based　PS　part　to　quencher　unit,　but　both　of　them　can　be　simultaneously　switched　on　by　cancer-related　biothiol　glutathione　(GSH)　in　phosphate　buffered　saline　(PBS)　solution　with　0.05%　Tween　80　as　a　result　of　cleavage　of　disulfide.　Also,　8a　exhibits　a　bright　fluorescence　image　and　a　substantial　ROS　production　in　A549　human　lung　adenocarcinoma,　HeLa　human　cervical　carcinoma　and　H22　mouse　hepatoma　cells　having　a　relatively　high　concentration　of　GSH,　thereby　leading　to　a　significant　photocytotoxicity,　with　IC50　values　as　low　as　0.44　mu　M,　0.67　mu　M　and　0.48　mu　M,　respectively.　In　addition,　the　photosensitizer　can　be　effectively　activated　and　imaged　in　H22　transplanted　hepatoma　tumors　of　mice　and　shows　a　strong　inhibition　on　tumor　growth.　All　these　results　suggest　that　such　a　GSH-responsive　photosensitizer　based　on　FRET　mechanism　may　provide　a　new　strategy　for　tumor-targeted　and　fluorescence　imaging-guided　cancer　therapy.　(c)　2020　Elsevier　Masson　SAS.　All　rights　reserved.