Abstract: Photoelectrochemical oxidation was applied to the treatment of berberine wastewater. The single and interactive effects of bias potential, initial pH, initial Cl^- concentration and reaction time were investigated according to the single-factor test and the response surface methodology based on central composite design. Furthermore, a second-order polynomial regression equation was developed to describe the TOC removal rate of photoelectrochemical oxidation process and validated by analysis of variance. The results demonstrated that the significance of influence factor followed the order: bias potential > initial Cl^- concentration > reaction time > initial pH, and the interactive influence between bias potential and initial Cl^- concentration was the most significant. The optimal conditions with the predicted TOC removal of 89.9% were determined as bias potential of 2.5 V, initial Cl^- concentration of 98.6 mmol/L, initial pH of 3.1 and reaction time of 3.6 h. Under these conditions, the actual TOC removal rate was 88.1%, which was highly consistent with the predicted result of the model equation.