The combination of persulfate, zerovalent iron, and UV radiation is an advanced oxidation process which allows for the degradation of high concentrations of organic dyes. This process is based on the generation of transient species with high oxidizing power, mainly the hydroxyl radical (HO•) and the sulfate radical (SO•-4). The reaction was carried out in a cylindrical glass reactor using potassium peroxydisulfate as an oxidant and zerovalent iron as a catalyst. The reaction was performed in a radiation chamber using a Philips HP-120 W lamp (λ ≥ 254 nm). A Box–Behnken design and response surface methodology were employed to evaluate the effect of persulfate dosage (0.01 (−1)–0.05 (+1) g L−1), iron dosage (0.01 (−1)–0.05 (+1) g L−1), pH (2 (−1)–11 (+1)), and reaction time (10 (−1)–120 (+1) min) on the reduction of 100 mg L−1 of Kraft Lignin. Optimization of the process determined that optimal experimental conditions were acidic pH (3.5), a persulfate concentration of 0.05 g L−1, a zerovalent iron concentration of 0.01 g L−1, and 60 min of reaction time, which resulted in 92% removal of Kraft Lignin, 96% chemical oxygen demand, 94% phenols, and 61.1% total organic carbon. The results indicate that the photocatalytic system was efficient in degrading a high concentration Kraft Lignin, and experimental design allowed determination of the maximum efficiency, with a 95% confidence interval.