Bio-oil obtained by the pyrolysis of woody biomass contains many oxygenated organic compounds which degrade the product quality and make necessary upgrading for its use as a liquid fuel. Hydrodeoxygenation (HDO) is a catalytic hydrotreating process for the removal of the problematic oxygen functionalities and is promising for bio-oil upgrading. In this work, 2-methyltetrahydrofuran (2-MTHF) was chosen as a model oxygenated compound, and its HDO reaction mechanism was studied on a silica-supported nickel phosphide catalyst (Ni 2 P/SiO 2 ) at a medium pressure of 0.5MPa. The temperature dependency of the catalyst activity was determined and it was found that at 350°C Ni 2 P/SiO 2 showed 100% conversion and 85% selectivity to n-pentane, with higher oxygen removal activity and less CC bond cracking activity than commercial noble metal Ru/C and Pd/Al 2 O 3 catalysts based on the same amount of active sites. A contact time study allowed the determination of a reaction sequence for 2-MTHF HDO on Ni 2 P/SiO 2 and it was found that CO bond cleavage of the furanic ring to generate either 2-pentanone or 1-pentanal was the rate-determining step. This was followed by hydrogen transfer steps to produce oxygen free compounds, n-pentane or n-butane. A partial pressure analysis of 2-MTHF and H 2 was consistent with a rate equation derived using a Langmuir–Hinshelwood (L–H) mechanism. This suggested that adsorption of 2-MTHF and hydrogen occurred competitively and that these species reacted on the Ni 2 P/SiO 2 surface. Although high partial pressure of H 2 was favorable for hydrogenation, too much H 2 competed with 2-MTHF adsorption, which caused lower conversion.