This work deals with the feasibility of ionic liquids (ILs) as an alternative drying agent to the conventional solvent (methanol) in the application of syngas dehydration. The screening of ILs by COSMO-RS model shows that [EMIM] [Tf2N] is the suitable absorbent for syngas dehydration among various possible ILs. The gas-liquid equilibrium (GLE) experiments for the CO (H-2)-[EMIM] [Tf2N] systems were carried out. The experimental data were compared with the predicted results by the UNIFAC-Lei model. The syngas drying experiments with [EMIM] [Tf2N] showed the excellent gas dehydration performance of ILs. On this basis, the conceptual process of syngas dehydration with [EMIM] [Tf2N] was simulated and optimized with the rigorous equilibrium stage (EQ) model, where the UNIFAC-Lei model parameters were embedded. It was found that the gas dehydration process with IL exhibits unique advantages in energy consumption, equipment cost, and dehydration performance when compared to the conventional benchmark methanol process. This work confirmed that ILs could be considered as promising alternatives to conventional solvents for syngas drying.