A systematical method is proposed for integrating the reaction and separation system and automatically identifying the optimal distillation sequence. Based on the regularity of each component as a non-key component, the non-key component matrix is constructed to illustrate the difference between distillation sequences. With the marginal minimum vapor rate of non-key components used to evaluate distillation sequences and the relation between reactor and distillation sequences considered, procedure is developed for automatically identifying the optimal distillation sequence and reactor parameters. The proposed method can be used for systems with simple columns performing sharp splits and the separated mixture can be taken as ideal mixtures. The reaction and distillation systems of the propylene oxide production process and styrene production process are analyzed, and the optimal distillation sequences generated by the proposed method are in good agreement with that identified by the systematical analyzation and rigorous simulation. (C) 2019 Elsevier Ltd. All rights reserved.