The alternative anodic-oxidation-coupled cathodic hydrogen evolution offers substantial potential for reducing energy consumption in hydrogen production. However, the fabrication of catalysts that maintain high activity and stability in integrated systems remains a significant challenge. Herein, we have developed an amorphous metal-metalloid alloy catalyst (NiCoBx) as anode for alkaline 5-hydroxymethylfurfural oxidation reaction (HMFOR) in integrated biomass electrooxidation-coupled hydrogen production system, which achieves a high current density of 400 mA cm−2 with a low cell voltage of 1.62 V. It saves ∼1.03 kWh/m3 of H2 produced and maintains excellent stability (>100 h). Operando/in situ spectroscopic characterization and theoretical analysis unveiled a “reactant-induced activation strategy” for NiCoBx: organic substrates with aldehyde groups preferentially adsorb on Co sites, reducing dehydrogenation adsorption energy and promoting the generation of Co3+ active sites. These insightful results present an inspiring outlook for the industrial application of biomass-coupled hydrogen production strategies.