The Fenton oxidation process was applied in the treatment of an actual high concentration nonylphenol Ethoxylates (NPEOs) wastewater. The effects of H 2 O 2 dosage, molar ratio of H 2 O 2 /Fe 2+ (Fe 2+ dosage), pH value and reaction time on the degradation of NPEOs were investigated. The orthogonal experiment indicated that the order of degree of influence on the COD removal was molar ratio of H 2 O 2 /Fe 2+ , reaction time, dosage of H 2 O 2 , and initial pH. The single-factor tests were carried out to determine the optimal conditions, and the results were H 2 O 2 dosage of 76.32 mmol/L, molar ratio of H 2 O 2 /Fe 2+ of 3, pH value of 5 and reaction time of 2 h. Under the optimum operation conditions, the COD removal efficiency was 85.6% and the effluent could be mixed with other wastewater into the large-scale biological treatment system.