Transformation of lignin-derived feedstocks into valuable hydrocarbons is of significant importance but still challenging. Herein, we report a novel and highly efficient bifunctional metal/acid CoMoS/γ-Al2O3 catalyst with doping of Nb2O5 for the hydrodeoxygenation of guaiacol. The dopant Nb2O5 significantly improves the HDO activity of CoMoS/γ-Al2O3 catalyst from 72.4% to 97.5% at 340 °C. Extensive characterizations confirm that the modification of Nb2O5 weakens the metal-support interaction, and thus improves the sulfidation degree of Mo species and the dispersion of MoS2 phases, leading to more MoS2 edges. Accordingly, the induced formation of more Brønsted acid sites originating from –SH on increased MoS2 edges greatly promotes the C(sp2)-O scissions of phenolics, and therefore enhances the yield of hydrocarbons especially benzene. This work focuses on the mechanistic insights into the effect of Nb2O5 on sulfided Mo-based catalyst in the HDO of lignin compound and provides a promising approach for facilitation of lignin valorization with extensive applications.