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 mu g/mL) under light illumination (670 nm, 1.5 J/cm(2)). Collectively, these results suggested that our nanospheres are the promising pH-responsive drug delivery systems for PDT.