Photodynamic therapy (PDT) is a widely-used technology for cancer therapy, but conventional photosensitizers still face some drawbacks, such as hydrophobicity, inadequate pharmacokinetics, low cell/tissue specificity, and uncontrollable photodynamic performance during the therapeutic process. Herein, we present a controllable photodynamic performance based on two-dimensional metal-organic frameworks (2D Zn-TCPP MOF) that displayed a week PDT effect under a neutral environment upon exposure to a 660 nm laser due to the degeneracy of Q bands of TCPP. However, the 2D Zn-TCPP MOF showed a significantly enhanced PDT effect in an acidic environment under irradiation with a 660 nm laser due to the released TCPP from decomposed MOF structure. From the in vitro outcomes, the 2D Zn-TCPP MOF showed controllable photodynamic performance from neutral to acidic environments. Due to the acidic tumor microenvironment, the 2D Zn-TCPP MOF presented the strongest antitumor effect in vivo under irradiation with a 660 nm laser. This work offers a promising strategy to develop a next-generation photosensitizer.