Distillation is the most commonly applied method of separating multicomponent mixtures. Distillation systems are highly energy intensive and always consume a large amount of energy to achieve the objective. In a computer-based optimization, many alternatives of distillation sequences may be examined by varying the values of related integer variables. In the present study, an algorithm that is a hybrid of Nonlinear Simplex and a genetic algorithm that is a stochastic method based on the stochastic generation of solution vectors was used to minimize the sum of the annual capital and exergetic cost of the alternative sequences. The results of the example cases show that the proposed algorithm is applicable for the determination the optimum alternative of the distillation sequences.