Chemical process simulation software is adopted to simulate the separation of ethyl acetate-dichloromethane-ethanol and water with the aim to use water as the extraction solvent and to meet the requirement of reuse. The influences of solvent ratio, reflux ratio, theoretical plate number, feed position, and solvent position on separation efficiency are discussed. Optimization of orthogonal design and response surface are employed to further optimize the parameters. Relative experimental results prove the reliability of the simulation.