Photodynamic　Therapy　(PDT)　is　recognized　for　its　exceptional　effectiveness　as　a　promising　cancer　treatment　method.　However,　it　is　noted　that　overexposure　to　the　dosage　and　sunlight　in　traditional　PDT　can　result　in　damage　to　healthy　tissues,　due　to　the　low　tumor　selectivity　of　currently　available　photosensitizers　(PSs).　To　address　this　challenge,　we　introduce　herein　a　new　strategy　where　the　small　molecule-targeted　agent,　erlotinib,　is　integrated　into　a　boron　dipyrromethene　(BODIPY)-based　PS　to　form　conjugate　6　to　enhance　the　precision　of　PDT.　This　conjugate　demonstrates　optical　absorption,　fluorescence　emission,　and　singlet　oxygen　generation　efficiency　comparable　to　the　reference　compound　7,　which　lacks　erlotinib.　In　vitro　studies　reveal　that,　after　internalization,　conjugate　6　predominantly　accumulates　in　the　lysosomes　of　HepG2　cells,　exhibiting　significant　photocytotoxicity　with　an　IC50　value　of　3.01　µM.　A　distinct　preference　for　HepG2　cells　over　HELF　cells　is　observed　with　conjugate　6　but　not　with　compound　7.　In　vivo　experiments　further　confirm　that　conjugate　6　has　a　specific　affinity　for　tumor　tissues,　and　the　combination　treatment　of　conjugate　6　with　laser　illumination　can　effectively　eradicate　H22　tumors　in　mice　with　outstanding　biosafety.　This　study　presents　a　novel　and　potential　PS　for　achieving　precise　PDT　against　cancer.　©　2024　by　the　authors.