Bio-oil is a sustainable energy source, produced from pyrolysis of lignocellulosic materials or algae. It is, however, difficult to directly use the bio-oil for fuels due to several drawbacks, such as its viscosities and high oxygen content. One of the ways to solve this is upgrading of the bio-oil through hydrodeoxygenation (HDO). In this study, guaiacol was used as a bio-oil model compound in HDO reaction via catalytic transfer hydrogenation. The reaction was conducted in the presence of TiO2-supported palladium catalysts, with isopropyl alcohol as a hydrogen source. Nickel and molybdenum were added into the Pd catalyst to investigate their effects on the catalyst activity. The prepared catalysts were characterized using XRD, N2 physisorption, hydrogen temperature-programmed reduction, and transmission electron microscopy. HDO reaction was carried out using a pressurized batch reactor at 250◦ C for 1 h with 30 bar of helium. Liquid products were analyzed by GC–MS and GC–FID to identify and quantify the conversions and product yields. The result showed that the presence of nickel on the catalyst could improve the catalytic activity of Pd/TiO2. Guaiacol conversion over Pd–Ni/TiO2 was 32.2%, while the conversion of guaiacol over Pd/TiO2 was only 17.9%. In addition, Pd–Ni/TiO2 showed good selectivity to produce cyclohexanol, while Pd/TiO2 showed good selectivity to produce one oxygenated compound such as 2-methylphenol and phenol.