Tailoring the hydrodeoxygenation capacity via construction of metal–support interfaces is still a significant challenge for hydrogenation of oxygenated substrates. Herein, we boosted the catalytic activity of the hydrogenation of methyl stearate by constructing a Ni1Fe1–ZnO interfacial structure instead of single Ni3Fe1 alloy. Multiple characterizations show that ZnO with low surface energy could encapsulate a NiFe alloy nanoparticle (∼14 nm) during hydrogen reduction, inhibiting the transformation of the fcc-Ni1Fe1 alloy to the fcc-Ni3Fe1 alloy structure. The Fe species of fcc-Ni1Fe1 alloy significantly promotes the electron transfer from NiFe alloy to ZnO, strengthening the adsorption of the CO bond. Furthermore, the Ni1Fe1–ZnO interface promotes the heterolytic cleavage of H2 to Hδ−, dramatically enhancing the hydrogenation activity of the positively charged carbonyl carbon, leading to a significant enhancement of catalytic activity in hydrogenation of methyl stearate to octadecanol by a factor of more than 30. This strategy of constructing metal–support interfaces could pave the way for the development of catalysts for hydrogenation of other polar functional groups.