The high-effect wastewater purification has become a serious problem for acetate ester production. The traditional technology for the separation of acetic acid and water including extractive distillation, azeotropic distillation and other methods, which is low efficiency in the selection of entrainer. Conductor-like Screening Model -Real Solvents (COSMO-RS) model can predict the thermodynamic properties of the fluid through quantitative calculation, which is helpful to select the high-effect entrainer for the acetic acid+water system, then simplifying operation and improving efficiency in the research. The latest research shows that organic solvents containing nitrogen and phosphorus have a good extraction effect on the water+acetic acid system. In this study, COSMO-RS model was applied to screen the high-effect entrainer for the separation of water+acetic acid system in extractive distillation, and the high-effect entrainer were specified in the ionic liquids composed of 5 phosphorus anions and 12 imidazole cations. The geometric structures of ions which were not included in COSMO software's original database were optimized by TURBOMOLE quantitative calculation module, and the solvent capacities of water in different ionic liquids, the selectivity of acetic acid to water in different ionic liquids, and the excess enthalpies when ionic liquids were mixed with water or acetic acid were analyzed. The results showed that the extraction effects of [MIM][DBP], [ODMIM][DEP], and [ODMIM][Me2PO4] were better than others. When water or acetic acid was mixed with ionic liquids, hydrogen bonding dominated the intermolecular interaction absolutely. Imidazole cations had strong ability to provide hydrogen bonding, and was easy to combine with acetic acid, so as to improve the relative volatility of water and acetic acid and achieve the purpose of separation. Comparing the excess enthalpy value, the interaction between [ODMIM]+ cation and acetic acid was the strongest intermolecular force. Finally, [ODMIM][DEP] was selected as the high-effective entrainer for the separation of water+acetic acid system. The results provide basic data for the separation of components in water+acetic acid system.