It is difficult to separate the methanol and hydrocarbons in the propylene oxide (PO) purification process due to their forming azeotrope. As for this, a novel PO separation process, in that the deionized water is employed as extractant and 1,2-propylene glycol (MPG) that is formed from the PO hydrolysis reaction is recovered, is presented in this work. The salient feature of this process is that both the non-catalyzed reactions of PO hydrolysis to form MPG and dipropylene glycol (DPG) are simultaneously considered and MPG by-product with high purity is obtained in virtue of the deionized water as reflux liquid and side take-off in MPG column. In addition, the ionic liquid (IL) extractant is screened through the conductor-like screening model for segment activity coefficient (COSMO-SAC) and the comparisons of separation efficiency between the IL and normal octane (nC8) extractant for the separation of PO and 2-methylpentane are made. With the non-random two-liquid (NRTL) thermodynamic model, the simulation and optimization design for the full flow sheet are performed and the effects of the key operation parameters such as solvent ratio, theoretical stages, feeding stage etc. on separation efficiency are detailedly discussed. The results show that the mass purity and the mass yield of PO can be up to 99.99% and 99.0%, and the condenser duty, reboiler duty and PO loss in the process with IL extractant can be decreased by 69.66%, 30.21% and 78.86% compared to ones with nC8. The total annual cost (TAC) calculation also suggests that the TAC would be significantly reduced if using IL in replace of nC8 for the investigated process. The presented results would provide a useful guide for improving the quality of PO product and the economic efficiency of industrial plant.