A ceria (CeO) promoted Cu-Ni bimetallic catalyst supported on SiO (Cu-Ni/CeO-SiO) was prepared and evaluated for catalytic hydrodeoxygenation (HDO) of vanillin. Silica supported monometallic Cu and Ni catalysts and bimetallic Cu-Ni catalyst (Cu/SiO, Ni/SiO, and Cu-Ni/SiO), without a ceria promoter, were also synthesized and tested for the same application. The highest conversion of vanillin was achieved with the Cu-Ni/CeO-SiO catalyst. Vanillyl alcohol was the sole product in the initial 2 h, followed by the formation of 2-methoxy-4-methylphenol, which was observed. Characterization of the synthesized catalysts revealed the presence of overlapping crystalline phases of CuO, NiO, and CeO on the Cu-Ni/CeO-SiO surface. We extended our study to find out the results of using CeO as the support of the Cu-Ni bimetallic catalyst (Cu-Ni/CeO). Partial incorporation of Cu and Ni cations into the ceria lattice took place, leading to the decrease of specific surface area and a concomitant compromise in the conversion. In the case of the Cu-Ni/CeO-SiO catalyst, the higher conversion was accredited to the facile formation of Cu active centers by the synergistic interaction between Ce/Ce and Cu/Cu redox couples and the incorporation of oxygen vacancies on the catalyst surface.