Compared to other petroleum, the natural gas combustion remains the cleanest and the one showing less CO2 emission. These reasons make the natural gas combustion one of the important issues to study. The separation of NGL is energy intensive. This operation is performed through a series of column including the debutanizer column. The present work is devoted to optimize the energy consumption at the level of the debutanizer column. The response surface technique and deploying a central composite numerical design is followed makes use of available data from a refinery. Using a multiple linear regressions, the optimization method leads us to three reliable models. Each of the three models takes as input the reflux ratio and the head pressure in order to predict the condenser heat duty, the reboiler heat duty and the purity of the produced butane. Suggested mathematical models were validated and their reliability was assessed via a set of statistical analyses. The optimization aims to simultaneously minimize the energy consumption of the condenser and reboiler, and maximize the purity of the ejected Butane. This optimization step allowed us to define the optimal values of reflux ratio and head pressure, with desirability function equal to 99 %. Under the determined optimal values, operating energy and cost of the industrial process were reduced by 38 % and 37 %, respectively, and besides, a high purity of butane was noticed reaching 99 %. From an economic point of view, separation NGL with optimal values of pressure and reflux ratio, may contribute to a decrease of CO2 emission and increases the energy efficiency.