The integration of reaction and extractive distillation system is beneficial for reducing the process cost. A systematic method is proposed to identify the optimal solvent, solvent-to-feed ratio, extractive distillation sequence and reactor operating conditions based on the integration of reactor and extractive distillation. The non-key component matrix method is used to generate the extractive distillation sequences. The proposed method can be used to evaluate different solvents, solvent-to-feed ratios, as well as the extractive distillation sequences; the optimal extractive distillation parameters corresponding to the minimum total annualized cost (TAC) can be identified considering different operating conditions. For the selective hydrogenation of benzene to cyclohexene process, the minimum total annualized cost of unit desired product, 4.01 $·kmol−1, is achieved when the reactor’s inlet temperature is 333 K, solvent N-Formylmorpholine and sequence S2 are employed, and the solvent-to-feed ratio is 4.