A　major　challenge　in　photodynamic　therapy　(PDT)　is　the　development　of　new　tumor-targeting　photosensitizers.　The　tumor-specific　activation　is　considered　to　be　an　effective　strategy　for　designing　these　photosensitizers.　Herein,　we　describe　a　novel　tumor-pH-responsive　supramolecular　photosensitizer,　LDH-ZnPcS8,　which　is　not　photoactive　under　neutral　conditions　but　is　precisely　and　efficiently　activated　in　a　slightly　acidic　environment　(pH　6.5).　LDH-ZnPcS8　is　prepared　by　using　a　simple　coprecipitation　method　based　on　the　electrostatic　interaction　between　negatively　charged　octasulfonate-modified　zinc(II)　phthalocyanine　(ZnPcS8)　and　cationic　hydroxide　layers　of　layered　double　hydroxide　(LDH).　The　in　vitro　photodynamic　activities　of　LDH-ZnPcS8　in　cancer　cells　are　dramatically　enhanced　relative　to　those　of　ZnPcS8　alone.　The　results　of　in　vivo　fluorescence　imaging　demonstrate　that　the　nanohybrid　is　activated　in　tumor　tissues,　where　it　displays　an　excellent　PDT　effect　resulting　in　95.3%　tumor　growth　inhibition.　Furthermore,　the　minimal　skin　phototoxicity　of　LDH-ZnPcS8　highlights　its　high　potential　as　a　novel　photosensitizer　for　activatable　PDT.　©　The　authors.