The Fenton process was used to treat the areca wastewater. Based on Box-Behnken response surface methodology, the primary focus of this paper is to evaluate simple and combined effects of the H2O2 dosage, FeSO4 dosage, initial pH value and the reaction time, establish a mathematical model between TOC removal rate and the above influence factors, and optimize the removal efficiency in Fenton ... [Show full abstract] process. When the conditions were the initial pH value of 5, H2O2 dosage of 50 mL/L, FeSO4 dosage of 12.5 g/L, the reaction time of 120 min, and 0.2% PAM dosage of 0.2 mL, the removal efficiency of TOC was 64.1%. The combined effect of H2O2 dosage, FeSO4 dosage was significant. Additionally, the effect of H2O2 dosage on the TOC removal rate was particularly significant. The optimum reaction conditions with the highest TOC removal ratio of 70.18% were determined to be H2O2 dosage of 54.2 mL/L, FeSO4 dosage of 12.55 g/L, initial pH value of 4.98, and reaction time of 103.5 min.