Abstract: Among chemical industrial wastewaters with high concentrations of organic compounds, wastewater from intermittent chlorpyrifos production with high organic concentration is particularly harmful to the environment and resistant to biodegradation. The ultrasonic-combined Fenton reaction is being assessed as a promising process for the treatment of refractory wastewater. A response surface method (RSM) was utilized to optimize the ultrasonic-combined Fenton process for industrial wastewater treatment. The results showed that:1) The center points of the response surface design were investigated in detail based on the effects of H₂O₂ dosage, Fe²⁺ dosage and reaction time on organic removal efficiency. H₂O₂ dosage, Fe²⁺ dosage and the reaction time were 0.5 mol/L, 0.93 g/L and 90 min, respectively. 2) A regressive model for COD_Cr removal efficiency in terms of H₂O₂ dosage, Fe²⁺ dosage and reaction time was developed based on a Box-Behnken Design (BBD). The analysis of variance indicated that the model was significant (P<0.0001). Fe²⁺ dosage had a greater effect on COD_Cr removal efficiency than the other two factors. Moreover, the interaction between Fe²⁺ dosage and reaction time was significant. 3) The relative error between the experimental results and the prediction of the model was 1.36% under the predicted optimum conditions (H₂O₂ dosage of 0.7 mol/L, Fe²⁺ dosage of 1.36 g/L, reaction time of 96 min). Effluent quality indexes were far below the grade 3 concentration limits established by the Integrated Wastewater Discharge Standard, and the ratio of B/C increased from 0.09 to 0.22. Moreover, the H₂O₂ and Fe²⁺ contents in each COD_Cr removal load were 0.14 mmol/mg and 0.28 mg/mg, respectively. The H₂O₂ and Fe²⁺ dosage in the wastewater treatment subjected to the combined process were relatively low. The ultrasonic-combined Fenton process was successfully applied for the pretreatment of the refractory organic wastewater with a favorable COD_Cr removal efficiency, and could improve the biodegradability of wastewater.