Separation of 1-butanol from the model fermentation broth (98 wt% water + 2 wt% ABE, acetone: 1-butanol: ethanol = 3: 6: 1) using liquid-liquid extraction (LLE) was investigated in this paper. This investigation involved multi-scale simulations from ab initio calculation to process simulation. Firstly, suitable extractant was screened from ionic liquids (ILs) combined of 30 anions and 40 cations using conductor-like screening model for real solvent (COSMO-RS) model. Meanwhile, the equilibrium experiment of the system ABE solution + selected IL was conducted to verify the screening result. From the screening, [HMIM] [FEP] was found to be an optimal extractant and the experimental data confirmed this screening result with a deviation of 3.54%. The continuous hybrid process consisting of extraction and distillation section with the selected IL was also simulated and compared with a referenced process selecting mesitylene as extractant using Aspen Plus to investigate the performance of IL in real industry. The simulated results showed that a higher mass purities and yields of acetone (>= 99.5 wt%), ethanol (>= 99.5 wt%) and 1-butanol (>= 99.9 wt%) could be obtained with much lower capital cost and energy consumption when the extractant was compared from [HMIM] [FEP] to mesitylene. The extractant consumption and the energy consumption could lower 10% and 4.4% in total, respectively. The ab initio calculation enabled a deep insight on the mechanism of IL in extraction. Obviously, the results uncovered by the ab initio calculation showed that interaction between IL and 1-butanol was much stronger than mesitylene.