Amines are an important class of compounds in natural products and medicines. The universal availability of amides provides a potential way for the synthesis of amines. Herein, Ru/Nb2O5 catalyst is demonstrated to be highly efficient and stable for the selective hydrogenation of propionamide to propylamine (as a model reaction), with up to 91.4% yield of propylamine under relatively mild conditions. Results from XPS analyses, CO chemisorption, TEM images and DRIFTS spectra revealed that the unique properties of Nb2O5 can effectively activate the C=O group of amides, and the smaller Ru particles on Nb2O5 could further promote the activation, leading to superior catalytic performance of Ru/Nb2O5 for amide hydrogenation. Meanwhile, reducing the surface acidity of Nb2O5 can greatly inhibit the side reactions to by-products, and further enhance the selectivity to amine. Moreover, this catalytic system is also applicable for the hydrogenation of a variety of amides and provides high potential for the industrial production of primary amines from amides.