Lignin　derivatives　are　one　class　of　attractive　alternative　feedstocks　for　the　production　of　renewable　biofuels.　Herein,　hydrodeoxygenation　(HDO)　of　lignin　derivatives　was　carried　out　using　a　single-atom　catalyst　(SAC)　comprised　of　Ni1　SAC　on　β-Mo2C.　A　number　of　lignin-derived　compounds　have　been　investigated,　and　nearly　100%　yield　of　biofuel　molecules　was　converted　from　various　lignin　derivatives　through　the　HDO　reaction,　demonstrating　that　Ni1/β-Mo2C　has　remarkable　potential　for　the　production　biofuels　through　catalytic　hydrodeoxygenation　of　lignin　derivatives.　The　reaction　mechanism　of　DHE　over　single-atom　catalyst　Ni1/β-Mo2C　was　confirmed　based　on　comprehensive　characterizations　of　catalysts　and　DFT　calculations.　Interestingly,　the　Ni　single-atom　active　sites　alter　the　reaction　pathway　by　shifting　the　geometry　of　the　adsorbed　intermediate　from　a　vertical　to　horizontal　conformation,　which　lowered　the　reaction　energy　barrier　and　improved　the　selectivity　to　biofuel　molecules,　resulting　in　extraordinary　catalytic　activity.　This　study　suggests　an　avenue　for　single-atom　catalysis　in　chemical　transformations　of　lignin　derivatives　into　biofuels.　©　2024　American　Chemical　Society.