A simple and rapid photoelectrochemical (PEC) sensor was developed for the label-free detection of a phosphoprotein (α-casein) based on a zirconium based porphyrinic metal–organic framework (MOF), PCN-222, which exhibited an enhanced photocurrent response toward dopamine under the O2-saturated aqueous media. In this work, in terms of PEC measurements and cyclic voltammetry, the PEC behaviors of PCN-222 in aqueous media were thoroughly investigated for the first time. Additionally, in the virtue of the steric hindrance effect from the coordination of the phosphate groups and inorganic Zr–O clusters as binding sites in PCN-222, this biosensor showed high sensitivity for detecting α-casein and the limit of detection (LOD) was estimated to be 0.13 μg mL–1. Moreover, the proposed method provides a promising platform for clinic diagnostic and therapeutics.