Hydrodeoxygenation reactions were studied with model compounds on sulfided hydrotreating CoMo/γ-Al2O3 and NiMo/γ-Al2O3 catalysts with and without adding a sulfur-containing compound into the reaction mixtures. Clear differences were observed in the behaviour of the model compounds. The addition of H2S improved the reactivity of methyl heptanoate and guaiacol with the formation of methanethiol but decreased that of phenol. The presence of sulfur compounds in the gas phase affected also the selectivities reducing the hydrogenation activity of the catalysts and shifting the C7/C6 hydrocarbon distribution from methyl heptanoate. Thus sulfur groups present on the catalyst surface form the key components for the reactions. The reaction network of methyl heptanoate can be described with two types of reactions: reactions with only hydrogen addition and reactions with the contribution of the surface SH- groups. We propose that the ability of the nucleophilic SH- groups to interact with model compounds is a primary factor influencing the initial overall reactivity of the starting compounds. Furthermore, the increasing amount of SH- groups directed the distribution of hydrocarbons towards C6 instead of C7 hydrocarbons from methyl heptanoate by accelerating the decarbonylation/decarboxylation reaction and the 1-hexanethiol formation.