This work firstly provides a thorough insight into the effects of the operating conditions (catalyst loading, initial H 2 pressure temperature, reaction time, H 2 /guaiacol ratio and liquid reaction volume) on the hydrodeoxygenation (HDO) of guaiacol over a Mo 2 C/CNF catalyst. Under the operating condition tested, gas and solid formation was negligible and guaiacol was primary converted to different liquid products, including non-deoxygenated (0-oxy), mono-deoxygenated (1-oxy) and fully deoxygenated (2oxy) compounds, together with high molecular weight soluble oligomers. An increase in the catalyst loading increased the guaiacol conversion and HDO efficiency, augmenting the proportions of HDO products. Among these species, the progressive transformation of 1-oxy compounds into 2-oxy species was kinetically and thermodynamically controlled by the catalyst loading and the amount of H 2 dissolved in the liquid medium, respectively. Augmenting the H 2 pressure increased the H 2 availability in the liquid, which led to increases over time in the guaiacol conversion and HDO efficiency, thus promoting the production of HDO products and facilitating the transformation of guaiacol into fully de-oxygenated products. This increase depended on the reaction volume, with more pronounced variations occurring for a small than for a large volume due to the greater variations occurring in the H 2 /guaiacol ratio for the former than the latter. The temperature exerted a kinetic promoting effect together with a thermodynamic inhibitory influence, as some of the reactions involved were not thermodynamically favoured at high temperature. Therefore, the detailed analysis included in this work brings novel information on guaiacol HDO, which can help to establish the basis for catalysts development and reactors design to achieve a sustainable bio-fuels production from lignocellulosic bio-oils.