The liquid-phase hydrodeoxygenation (HDO), catalyzed by metal or metal-acid sites, provides an effective catalytic strategy to remove oxygen-containing functionalities of lignin-derived phenolic compounds on the route to fuels and chemicals. Developing the catalyst with high activity and stability is crucial for such a chemical process but still remains a significant challenge. In this contribution, highly dispersed subnanometric Ru metal clusters (< 1.5 nm) encapsulated in the cavities of MWW zeolites, including MCM-22 and its siliceous analog ITQ-1, have been developed for the HDO of guaiacol, an important lignin-derived phenolic monomer, in an apolar liquid phase under mild conditions (160°C, 3 MPa H2). We validate the effective encapsulation of Ru metal clusters in ITQ-1 and HMCM-22 zeolites cavities via complementary characterization methods. The detailed reaction pathways of the HDO of guaiacol are depicted by using guaiacol, phenol, and anisole as reactants. The subnanometric Ru metal clusters confined in MWW zeolite thin layers (20-30 nm in thickness) show remarkable enhancement in HDO activity compared to the large metal particles. The close proximity between Ru metal clusters and Brønsted acid sites (BAS) confined in zeolite constraints delivers a synergistic effect, leading to an additional enhancement in catalytic activity as well as product selectivity. The super stability of the ultrafine Ru metal clusters against sintering and leaching after successive catalytic runs is achieved. The well-defined mono-or bi-functional Ru-containing MWW zeolite catalysts enable the fundamental understanding of HDO of lignin-derived phenolic compounds in the apolar liquid phase and 2 also provide a prototype for the design of superior catalysts for the other energy-related transformations.