The advanced oxidation technology, ferrous ion (Fe(II)) activated persulfate (PS) producing sulfate radicals, was used for the advanced treatment of effluent from an integrated wastewater treatment plant in a papermaking industrial park. Separate and interactive effects of PS dosage, Fe(II)/PS ratio and initial pH on chemical oxygen demand (COD) removal were analyzed by the response surface methodology (RSM). The results showed that Fe(II)-PS system was effective in COD removal from the secondary effluent. PS dosage was the most dominant factor with positive influence on COD removal, followed by initial pH value. The optimum conditions with COD removal of 54.4% were obtained at PS/COD of 2.2, initial pH of 6.47 and Fe(II)/PS of 1.89. UV-visible spectrum analysis showed that after RSM optimization, Fe(II)-PS system effectively degraded large organic molecules into small ones, and decreased humification degree of the effluent. Three-dimensional fluorescence analysis demonstrated that aromatic protein and fulvic substances were fully decomposed by the Fe(II)-PS treatment.