Abstract: To address the issue of high energy consumption in tail gas treatment units of natural gas purification plants, this research proposes an optimization method that combines process simulation with statistical data analysis. Initially, the Plackett-Burman （PB） experimental design was employed to identify the key factors that significantly affect the energy consumption of tail gas treatment unit. Subsequently, the Box-Behnken Design （BBD） response surface methodology was used to optimize the tail gas treatment process. Finally, the effectiveness of the BBD optimization method was validated through simulation analysis. The results indicated that number of absorber stages, lean amine circulation rate, rich amine temperature to regenerator, and regenerator reflux ratio were the most significant factors affecting the energy consumption of tail gas treatment unit. The order of significance of these factors was as follows: lean amine circulation rate > regenerator reflux ratio > rich amine temperature to regenerator > number of absorber stages. The optimal process conditions determined were: number of absorber stages was 10, lean amine circulation rate was 90 000 kg·h⁻¹, rich amine temperature to regenerator was 100 °C, and regenerator reflux ratio was 3.0. Under the optimized conditions, the energy consumption of the tail gas treatment unit could be reduced by 31.63%. The relative error between the software simulation value and the model prediction value was only 0.07%, confirming the accuracy and reliability of the established energy consumption model for the tail gas treatment unit. The research conclusions can provide a reference for energy optimization of tail gas treatment units in actual natural gas purification plants.