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Metal-oxide interaction was widely observed in supported metal catalysts, playing a significant role in tuning the catalytic performance. Here, we reported that the interaction of Ru and MnO x was able to facilitate the hydrodeoxygenation of levulinic acid (LA) to 2-butanol with a high turnover frequency (1.99 × 10 6 h -1 ), turnover number (4411), and yield (98.8%). Moreover, this catalyst was capable of removing the hydroxymethyl group of lactones and diol with high yields of products. The high activity of the Ru-MnO x catalyst was due to the strong Ru-MnO x interaction, which facilitated reduction of Ru oxide to Ru 0 and Mn oxide to Mn 2+ . The increased fractions of Ru 0 and Mn 2+ provided metal and Lewis acid sites, respectively, and therefore facilitated LA hydrodeoxygenation. A linear correlation between the hydrodeoxygenation activity of the Ru-MnO x catalyst and [Mn 2+ ]ln([Ru 0 ]) was observed.