Abstract: By using the pinch analysis method in the heat exchanger design of heat integrated complex distillation system synthesis，a mixed-integrated nonlinear programming (MINLP) model with the continuous variables of the recoveries of key components in the pre-fractionators and reflux ratios and the discrete variables of separation sequence and thermal-coupling scheme was established. The solution of the problem could be achieved with an improved simulated annealing algorithm. Three example problems of five-component mixtures separation were solved and the optimized parameters and economic benefits of different optimal schemes were analyzed and compared. The results demonstrated that the system annual total cost could be reduced by using the heat integrated complex distillation configuration. The solutions of example problems also demonstrated that the proposed method was efficient for the heat integrated complex distillation synthesis problem.