Lysosomes　are　promising　therapeutic　targets　for　cancer　therapy　due　to　their　essential　function　and　increased　vulnerability　in　cancer　cells.　Herein,　we　report　a　new　category　of　cationic　photosensitizers　(compounds　1–3)　containing　a　quaternary　ammonium　group.　These　photosensitizers　exhibited　selective　uptake　on　cancer　cells　(about　three　times　compared　to　the　normal　cells),　lysosome-specific　localization　(Pearson＇s　coefficients　greater　than　0.85),　remarkable　phototoxicity　(IC50　are　in　the　range　of　dozens　of　nM),　and　at　the　same　time,　favorable　biosafety.　Mechanically,　these　tumor-targeting　photosensitizers　function　as　light-controlled　“bombs”,　inducing　lysosomal　membrane　permeabilization　(LMP),　ultimately　resulting　in　apoptosis　of　cancer　cells.　In　vivo,　compound　1　(a　representative　of　these　novel　photosensitizers)　accumulated　predominantly　in　and　visualized　tumors　implanted　on　mice.　Upon　exposure　to　near-infrared　light　irradiation　(50　J/cm2),　the　compound　effectively　ablated　the　tumor　at　a　low　dose　of　2　mg/kg.　Our　results　demonstrate　a　novel　class　of　photosensitizers　showing　potential　for　integrated　cancer　diagnosis　and　photodynamic　treatment.　©　2024　Elsevier　B.V.