It　is　urgently　required　to　develop　the　molecular　agents　with　high　therapeutic　efficacy　and　low　side　effects　for　precise　cancer　therapy.　Herein,　an　advanced　multifunctional　prodrug　B-BDP-CL-CPT,　consisting　of　a　glutathione　(GSH)-responsive　boron　dipyrromethene　(BDP)-based　photosensitizer,　a　chemo　drug　camptothecin　(CPT),　a　reactive　oxygen　species　(ROS)-sensitive　chain　linking　BDP　with　CPT,　and　a　biotin　fragment　with　specific　affinity　to　biotin-receptor,　was　designed　and　synthesized.　Owing　to　the　introduction　of　2,4-dinitrobenzenesulfonate　(DNBS)　as　the　quencher　into　BDP　core　and　chemical　modification　of　CPT　at　the　active　site,　B-BDP-CL-CPT　is　non-cytotoxic.　Having　biotin　as　the　targeting　ligand,　the　prodrug　can　be　efficiently　internalized　by　biotin-acceptor　positive　cancer　cells,　and　then　activated　to　generate　substantial　light-induced　ROS　through　removal　of　the　stopper　DNBS　by　intracellular　GSH　which　is　abundant　in　cancer　cells.　The　resulting　ROS　can　not　only　serve　for　photodynamic　therapy　(PDT)　but　also　further　cleave　thioketal　linkage　causing　the　release　of　CPT,　to　achieve　dual　PDT　and　chemotherapy.　And　the　combination　of　preferential　accumulation　with　specific　activation　in　tumor　tissues　for　this　prodrug　is　conducive　to　improving　the　dual　therapeutic　outcome　meanwhile　greatly　reducing　the　photo-damage　and　the　release　of　CPT　in　adjacent　healthy　tissues.　In　addition,　the　activated　B-BDP-CL-CPT　can　give　bright　fluorescence　signals　which　are　favor　for　imaging-guided　PDT　and　real-time　tracking　the　release　of　therapeutic　agent.　The　in　vitro　and　in　vivo　investigations　have　been　performed　to　demonstrate　the　targeted　and　combined　anticancer　activities　of　this　prodrug　against　HepG2　and　HeLa　cancer　cells,　and　the　mice　with　H22　tumors.　This　study　proposes　a　new　tactics　for　highly　efficient　and　precise　cancer　treatment.　©　2022　Elsevier　Ltd