Currently, rapidly increasing consumption of fossil resources has propelled the upgrading of biomass as an alternative and sustainable technology to produce important chemicals and bio-oils. In this regard, the rational design of low-cost and robust supported metal-based catalysts that exhibit excellent catalytic hydrodeoxygenation (HDO) performance for the conversion of biomass is quite necessary. Herein, we developed hierarchical flower-like nitrogen-doped carbon layer-coated bimetallic Ni-Co nanoparticles, which were distributed over the carbonaceous matrix (NixCo@NC@C), via a metal-organic framework (MOF) ZIF-67 precursor approach, assisted by the etching of Ni2+ ions, hydrothermal treatment together with glucose, and following carbonization processes. The as-fabricated Ni3Co@NC@C catalyst bearing a 3 : 1 Ni/Co molar ratio showed a superior catalytic HDO activity towards aqueous phase HDO of vanillin to other bimetallic NiCo catalysts with different Ni/Co molar ratios under mild reaction conditions, along with a 100% selectivity to 2-methoxy-4-methylphenol at a full vanillin conversion, despite its smaller number of exposed metallic sites. It was revealed that over the Ni3Co@NC@C catalyst, the surface abundant defective oxygen vacancies and electron-rich Co0 species were conducive to the adsorption and activation of vanillin and the reaction intermediate, thereby giving rise to the outstanding catalytic activity. Moreover, for Ni3Co@NC@C, the adequate protection effect of surface carbon layers, as well as the unique hierarchical flower-like microstructure, could significantly inhibit the leaching of active metal species in the reaction medium, thereby leading to high structural stability. The present findings afford a promising strategy for constructing low-cost and robust carbon-supported bimetallic catalysts for the HDO of lignin-derived derivatives.