We report a highly efficient bifunctional catalyst, Pd/SO₃H-MIL-101(Cr), consisting of Pd nanoparticles immobilized on a mesoporous sulfonic acid-functionalized metal–organic framework SO₃H-MIL-101(Cr), which exhibits high catalytic performance in promoting biomass refining. The use of SO₃H-MIL-101(Cr) as a support renders highly dispersed Pd nanoparticles with uniform size distribution, sufficient reactant contact in aqueous media, and rapid activation of the reactants induced by the Brønsted acid coordination sites (sulfonic acid groups from SO₃H-MIL-101(Cr)). Thus, the 2.0 wt% Pd/SO₃H-MIL-101(Cr) catalyst exhibits novel synergy in the hydrodeoxygenation of vanillin (a typical model compound of lignin) at low H₂ pressure under mild conditions in aqueous media. Excellent catalytic results (100% conversion of vanillin with exclusive selectivity for the 2-methoxy-4-methylphenol product) could be achieved, and no loss of catalytic activity and selectivity was observed after seven recycles in succession.