The selective hydrodeoxygenation (HDO) of amides is a key methodology to producing amines, yet it remains a great challenge due to the highly stable amide molecular structure. In this study a series of 2RuxMo/SiO2 (x = 0 ∼ 3) catalysts were prepared with sequential impregnation method followed by reduction. The reaction tests showed that the target amine yield presented a volcano-shape dependence on the Mo content, and reached the highest value at the Mo content of 0.2 wt% which corresponded to a Mo/Ru atomic ratio of 0.11 and a Mo surface density of 0.08. By contrast, a higher Mo content resulted in dramatic decrease in both activity and selectivity. By using HAADF-STEM, X-ray absorption spectroscopy (XAS), H2-TPR and CO-chemisorption, the structure of the best-performance 2Ru0.2Mo/SiO2 catalyst was identified as Ru NPs of ∼ 2 nm decorated with mononuclear Mo5+Ox species, which was in contrast with the polymeric MoO2-like species partially covering the Ru surface for the 2Ru3Mo/SiO2. Kinetic studies revealed that the reaction order with respect to CyCONH2 was 1.2, −0.1 and −0.5 over the 2Ru/SiO2, 2Ru0.2Mo/SiO2 and 2Ru3Mo/SiO2, respectively, which indicated amide was selectively activated on the low-coordinated Mo5+Ox sites while H2 was activated on the Ru sites and the reaction proceeded at the Mo-Ru interface. The turnover frequency based on interfacial Ru-Mo sites reached 407.8 h−1, which was more than twofold higher than that of Ru-W system (175.6 h−1) we previously reported.