A series of SiO2-TiO2 binary oxides supported high loading Ni catalysts were prepared using the co-precipitation method and tested in guaiacol hydrodeoxygenation (HDO). The catalysts were characterized using N-2 adsorption-desorption, XRD, TEM, FT-IR, XPS, H-2-TPD, and NH3-TPD. The formation of Si-O-Ti bond in the SiO2-TiO2 binary oxides was verified by XPS, which can increase the total amount of acidic sites and enhance the interaction between metal Ni and TiO2. The oxygen defect sites of TiO2 were formed near the perimeter of the metal-support interface, leading to generation of Ni delta--O-v-Ti-3+ interface sites, which play the role of active centers to catalyze guaiacol HDO. These positive factors promoted HDO activity over Ni catalysts supported on binary oxides, compared to Ni loaded on single oxide supports. The selectivity of products indicates relatively high temperature and low H-2 pressure are beneficial for producing oxygen-free aromatics in HDO of guaiacol.