The hydrogenation of lignin-derived phenolics to produce valuable chemicals is a promising but challenging task. This study successfully demonstrates the use of sustainable transition metal-based catalysts to hydrogenate lignin-derived phenolics. A defect-induced oxygen vacancy containing H-NbOx prepared from commercial Nb2O5 was employed as a catalyst. H-NbOx exhibited higher oxygen vacancies (158.21 μmol/g) than commercial Nb2O5 (39.01 μmol/g), evaluated from O2-TPD. Upon supporting 10 wt % Ni, a Ni/NiO interface was formed over H-NbOx, which was intrinsically active for the hydrogenation of phenolics. 10Ni/H-NbOx exhibited a two-fold increase in activity than 10Ni/Nb2O5, achieving >99% eugenol conversion and affording ∼94% 4-propyl cyclohexanol selectivity, wherein ∼63% eugenol conversion and ∼73% 4-propyl cyclohexanol selectivity were obtained over 10Ni/Nb2O5. The Ni/NiO formation was confirmed by X-ray photoelectron spectroscopy, HR-TEM, and H2-TPR analysis, while the oxygen vacancies were verified by Raman spectroscopy and O2-TPD analysis. The resulting interface enhanced the synergy between Ni and H-NbOx and facilitated hydrogen dissociation, confirmed by H2-TPD. Remarkably, 10Ni/H-NbOx maintained its catalytic activity for five tested cycles and demonstrated exceptional activity with various phenolics. Our findings highlight the potential of a sustainable transition metal catalyst for the hydrogenation of lignin-derived phenolic compounds, which could pave the path to producing valuable chemicals in an environmentally friendly manner.