Abstract: Response surface methodology(RSM) was employed to obtain the optimization experiment conditions of the Fenton degradation treatment of liquid scintillation waste. 5 factors central composite design with RSM was used, in which the factors are FeSO₄ concentration, H₂O₂ concentration, pH, time and temperature, while the waste sample’s total COD removal rate was chosen as the response. Coefficient of determination R² is 0.938 1 and adjust coefficient of determination R²_Adj is 0.880 1, which indicate that the model fits well and predicates the Fenton degradation process well. The optimal experiment conditions are that the initial Fe²⁺ concentration is 0.99 mmol/L, and the initial H₂O₂ concentration is 57.50 mmol/L, and pH is 2.48, and  the temperature is 76.59 ℃, and the reaction time is 68.53 minutes. Under these optimal experiment conditions, the predicted maximum COD removal rate is 87.19%, and the actual COD removal rate of the waste sample is 85.81% (n=3). The relative error is 1.58%, which indicate that RSM is suitable for the design and optimization of the Fenton oxidation processes.