CeO2 was employed to modify the Cu/SiO2 catalyst for water-gas shift (WGS) reaction, and two different ways to introduce CeO2 were applied, i.e., ammonia evaporation hydrothermal (AEH) and impregnation (IM) methods. The sizes of Cu nanoparticles and strength of Cu-SiO2 synergetic interaction were analyzed by HRTEM and H-2-TPR characterizations. The Cu+/Cu-0 ratio and strength of Cu-CeO2 synergetic interaction were evaluated via XPS and XAES techniques. It was revealed that more Cu-0 leads to higher CO conversion, based on its pronounced effect on water dissociation. The strength of the Cu-SiO2 synergetic interaction in the Cu/SiO2 catalyst varies with altering the state of CuO species. Cu-CeO2 synergetic interaction is associated with oxygen vacancies in CeO2, which also act as active sites for H2O dissociation. The Cu/SiO2-CeO2-AEH catalyst exhibits the best activity and stability among the three catalysts toward the WGS reaction, because it has a large number of Cu-0 and strong synergetic interaction of Cu with SiO2 and CeO2.