To　improve　the　aqueous　solubility　and　cancer　targeting　of　the　photosensitizers　in　photodynamic　therapy　(PDT),　we　encapsulated　the　photosensitizer　in　a　biocompatibility　and　pH-sensitive　drug　delivery　system,　zeolitic　imidazolate　frameworks-8　(ZIF-8)　nanospheres.　Powder　X-ray　diffraction　and　electron　microscopy　show　that　our　nanospheres　are　uniform　and　single-crystalline　particles.　Owing　to　the　cleavage　of　zinc–ligand　coordination　bonds,　more　ZnPc–COOH　were　released　much　faster　in　the　mild　acidic　conditions　(pH　5.0　and　6.0)　in　comparison　with　physiological　environment　(pH　7.4).　By　incorporating　ZnPc–COOH　in　ZIF-8,　our　nanospheres　exhibited　high　singlet　oxygen　quantum　yield　and　intracellular　ROS　generation.　Cell　viability　experiments　toward　HepG2　cells　demonstrated　the　low　toxicity　of　ZIF-8　and　the　good　anticancer　efficacy　of　the　nanospheres　with　low　IC50　values　(4.2–4.9 μg/mL)　under　light　illumination　(670 nm,　1.5 J/cm2).　Collectively,　these　results　suggested　that　our　nanospheres　are　the　promising　pH-responsive　drug　delivery　systems　for　PDT.　©　2017,　Springer　Science+Business　Media,　LLC.