DME synthesis from syngas via methanol has been carried out in a single-stage liquid phase reactor. Cu/ZnO/Al2O3 and γ-Al2O3 were used together as methanol synthesis catalyst and dehydration catalyst, respectively. The influence of water on the catalytic system was investigated mainly. Water affected the activity of methanol dehydration catalyst as well as methanol synthesis catalyst. Thus, removal of water from the reaction system, by adding a dehydrating agent or controlling methanol formation rate by the reaction parameters, was efficient in maintaining the high catalytic activity and stability.