Development　of　the　drug　with　high　therapeutic　efficacy　and　low　toxicity　is　crucial　to　cancer　ablation.　In　this　study,　we　have　demonstrated　a　red　light-responsive　prodrug　BDP-TK-CPT　by　connecting　the　chemotherapeutic　agent　camptothecin　with　a　boron　dipyrromethene　(BDP)-based　photosensitizer　via　a　reactive　oxygen　species　(ROS)-labile　thioketal　chain.　Since　camptothecin　is　modified　by　a　BDP-based　macrocycle　at　the　active　site,　the　formed　prodrug　displays　an　extremely　low　toxicity　in　dark.　However,　upon　illumination　by　red　light,　it　can　efficiently　generate　ROS　leading　to　cell　death　by　photodynamic　therapy.　Meanwhile,　the　ROS　generated　can　destroy　thioketal　group　to　release　free　camptothecin　which　further　results　in　local　cell　death　by　chemotherapy.　The　combined　antitumor　effects　of　the　prodrug　have　been　verified　in　HepG2,　EC109,　and　HeLa　cancer　cells　and　mice　bearing　H22　tumors.　This　study　may　provide　an　alternative　strategy　for　stimuli-responsive　combination　treatment　of　tumors　by　conjugation　of　ROS-activatable　prodrugs　with　photosensitizing　agents.　(C)　2021　Elsevier　Masson　SAS.　All　rights　reserved.