The compound 3,5,6-trichloro-2-pyridinol (TCPy), a metabolite of the broad-spectrum organophosphorus insecticide chlorpyrifos, is both more persistent and more water soluble than its parent compound. This difference, which allows TCPy to more readily leach into surface water and groundwater, has led to widespread contamination of TCPy in soils and aquatic environments. In this study, the degradation of TCPy by sulfate radicals was evaluated using zero valent iron activated persulfate in aqueous media. Response surface methodology coupled with Box-Behnken design was applied to evaluate the effects of the independent variables (concentration of zero valent iron, concentration of persulfate, and pH) on the mineralization of TCPy by zero valent iron activated persulfate system. The interactions, coefficients, and residuals of these variables were statically evaluated by analysis of variance. Based on the model, the optimum conditions for maximum TCPy mineralization were determined as 10.4mM of persulfate, 1.2 g/L of zero valent iron and an initial pH of 3.2. The reaction kinetics of the degradation process were examined as functions of persulfate concentration, zero valent iron concentration, and pH. Results show that zero valent iron activated persulfate can effectively remove TCPy in water with a high mineralization rate of up to 81.1%. The degradation pathways of TCPy were proposed based on the products identified by GC-MS. Calculated 꺎G values using density functional theory agreed with the proposed experimental pathway.