A　supermolecular　photosensitizer　with　excellent　anticancer　behavior　when　used　for　photodynamic　therapy　(PDT)　is　fabricated　by　the　incorporation　of　zinc　phthalocyanines　(ZnPc)　into　the　gallery　of　a　layered　double　hydroxide　(LDH).　The　composite　material　possesses　uniform　particle　size　(hydrodynamic　diameter　∼120　nm),　and　the　host-guest　and　guest-guest　interactions　result　in　a　high　dispersion　of　ZnPc　in　a　monomeric　state　in　the　interlayer　region　of　the　LDH　matrix,　with　high　singlet　oxygen　production　efficiency.　In　vitro　tests　performed　with　HepG2　cells　reveal　a　satisfactory　PDT　effectiveness　of　the　ZnPc(1.5%)/LDH　composite　photosensitizer:　a　cellular　damage　as　high　as　85.7%　is　achieved　with　a　rather　low　dosage　of　ZnPc　(10　μg/mL).　An　extraordinarily　high　specific　efficacy　is　demonstrated　(31.59　μg-1　(J/cm2)　-1),　which　is　over　185.5%　enhancement　compared　with　the　previously　reported　photosensitizers　under　similar　test　conditions.　Furthermore,　an　in　vivo　study　of　the　ZnPc(1.5%)/LDH　demonstrates　excellent　PDT　performance　with　an　ultra-low　dose　(0.3　mg/kg)　and　a　low　optical　fluence　rate　(54　J/cm2).　In　addition,　the　ZnPc/LDH　photosensitizer　displays　high　stability,　good　biocompatibility,　and　low　cytotoxicity,　which　would　guarantee　its　practical　application.　Therefore,　this　work　provides　a　facile　approach　for　design　and　fabrication　of　inorganic-organic　supermolecular　materials　with　greatly　enhanced　anticancer　behavior.　By　incorporating　zinc　phthalocyanines　(ZnPc)　into　the　gallery　of　a　layered　double　hydroxide　(LDH),　a　supermolecular　photosensitizer　is　fabricated　which　can　serve　as　a　promising　photosensitizer　in　the　field　of　photodynamic　therapy　(PDT)　with　excellent　anticancer　behavior,　good　biocompatibility,　and　low　cytotoxicity.　©　2014　WILEY-VCH　Verlag　GmbH　&　Co.　KGaA,　Weinheim.