The high porosity and tunability of metal-organic frameworks (MOFs) have made them an appealing group of materials for environmental applications. However, their potential in the photocatalytic degradation of per- and polyfluoroalkyl substances (PFAS) has been rarely investigated. Hereby, we demonstrate that over 98.9% of perfluorooctanoic acid (PFOA) was degraded by MIL-125-NH2, a titanium-based MOF, in 24 h under Hg-lamp irradiation. The MOF maintained its structural integrity and porosity after three cycles, as indicated by its crystal structure, surface area, and pore size distribution. Based on the experimental results and density functional theory (DFT) calculations, a detailed reaction mechanism of the chain-shortening and H/F exchange pathways in hydrated electron (eaq-)-induced PFOA degradation were revealed. Significantly, we proposed that the coordinated contribution of eaq- and hydroxyl radical (•OH) is vital for chain-shortening, highlighting the importance of an integrated system capable of both reduction and oxidation for efficient PFAS degradation in water. Our results shed light on the development of effective and sustainable technologies for PFAS breakdown in the environment.