In this work, the mechanism and intrinsic reaction energy barriers of hydro-deoxygenation (HDO) of anisole, as key stage of the catalytic decomposition over metal-loaded acid support catalysts (bi-functional catalysts), were investigated by Density Functional Theory (DFT). Common transition metals were compared in terms of their adsorption energy when adsorbing anisole molecule for the selection of loading metals. The roles of metal and acid sites in the HDO of phenolic compounds (Phs) over bi-functional catalyst were investigated, and a novel HDO mechanism was proposed by combining Fukui index and bond orders of phenol molecule analyses. HDO reactions of Phs over sole acid sites and the bi-functional catalysts were modelled. The modelling results revealed that, for anisole adsorption, Co, Mo, Ni and Cu showed higher adsorption energy than other transition metals. Molecule analysis results showed that HDO over bi-functional catalysts was dominated by the protonation of the hydroxyl group on Phs. Reaction modelling exhibited that active metals had significant effects in lowering energy barriers of the reactions for all the Phs; the metal active sites facilitated the protonation by developing strong interaction with the adsorbed reactant, and they also aid the hydrogen molecule dissociation. Ni and Mo showed the best catalytic effect on the HDO for most Phs. The effect of side chain methyl substitutes on the HDO reactions for various Phs intermediates during anisole decomposition was also investigated by reaction modelling. Modelling results in this study were found in good agreement with experimental data.