Zero liquid discharge (ZLD) of coal chemical wastewater is a significant strategy for sustainable management of water resources. Efficient removal of phenols has high significance for the realization of ZLD. In this study, a method of structural characteristics integrated computer-aided molecular design (CAMD) is used for phenols removal considering synergistic effect. Solvent mixture for synergistic extraction of phenols by using methyl propyl ketone (MPK) in combination with n-pentanol is proposed with the volume ration of MPK to n-pentanol 8:2. Using solvent mixture (80% MPK, 20% n-pentanol), the phenols removal efficiencies are observably better than that using methyl isobutyl ketone (MIBK) or diisopropyl ether (DIPE). The total phenols concentration of coal gasification wastewater can be removed from 6273 mg/L to less than 300 mg/L after two-stage extraction. In addition, solvent mixture (MPK, n-pentanol) can also achieve the total phenols target if the volume fraction of n-pentanol was no more than 70%, the wide range volume fraction of which has potential application in industry.