Cylcohexanol is an essential bulk chemical that can be produced via cyclohexene hydration, a liquid-liquid two-phase reaction that is limited by the low reaction rate and the equilibrium conversion. Adding an appropriate solvent is the most promising method to break through these limitations. However, in previous works the solvent was almost blindly selected without a global consideration. In this work, a rational multiscale method is proposed for the effective selection of an economical and sustainable solvent for the direct hydration of cyclohexene. At the molecular scale, liquid-liquid phase equilibrium was estimated using group contribution methods to rapidly screen the potential solvent candidates from a range of organics, based on the partition coefficient. At the reactor scale, the candidates were experimentally investigated to pick out the solvents that could significantly improve the conversion, without introducing side reactions or deactivating the catalyst. At the process scale, the total annual cost (TAC), CO₂ emission, and other metrics were calculated to evaluate the eco-efficiency of all solvents. Using this multi-scale method, acetophenone was selected as an eco-efficient solvent from over 100 organics, resulting in the reduction of TAC by 8 % and CO₂ emission by 17 % in the production process. Using acetophenone also led to the increase of cyclohexanol yield from 12.3 % to 27.6 % without the occurrence of side reactions and catalyst deactivation.