Biomass-derived 2-methyltetrahydrofuran (2-MTHF) is a significant green solvent and a promising biomass fuel, and it is usually produced from 2-methylfuran (2-MF) hydrogenation in liquid phase. It is highly desirable and challenging to develop vapor-phase hydrogenation with such a catalyst that combines high efficiency, excellent stability, easy scale up and low cost. In the present work, we prepared three Ni/SiO2 catalysts using impregnation, urea-assisted impregnation, and deposition–precipitation methods (labeled as NS-IM, NS-UIM, and NS-DP), respectively, for the synthesis of 2-MTHF from 2-MF hydrogenation in vapor-phase. The NS-DP catalyst demonstrated the highest activity and the best stability among all catalysts. Under moderate reaction conditions, a 2-MF conversion of 99.9% with a 2-MTHF selectivity of 99% were achieved on the NS-DP catalyst over 140 h, and it showed a potential significant application prospect. N2 physisorption, ICP, XRD, H2-TPR, TG, HRTEM, and in situ XPS characterization revealed that the catalyst prepared by the deposition–precipitation method possessed the smallest Ni grain size and the strongest metal-support interaction, leading to the highest performance. It was demonstrated that reaction pressure affected the conversion of 2-MF while the reaction temperature affected the selectivity of 2-MTHF. In addition, the structures of the spent catalysts were characterized, and mechanism of deactivation have been discussed in this work.