The nanoengineering of efficient and stable nanocatalysts is highly desired for sustainable biomass valorization toward the selective hydrogenation of furfural. The interaction of supports with metallic nanoparticles and oxygen vacancies has a significant role in the catalytic activity of oxide nanocatalysts. Here, by combining density functional theory (DFT) calculations and catalytic experimental data, we demonstrated that the presence of TiO 2 in Ru−SiO 2 catalysts might allow an association between oxygen vacancies and the hydrogen spillover effect. Specifically, Ru−TiO 2 −SiO 2 and Ru−SiO 2 nanocatalysts displayed improved activities and selectivities toward the reaction mentioned above. The nanomaterials were prepared by a simple, versatile, and single-step modified sol− gel process build upon two different stabilizing agents (P123 and CTAB), which afforded entirely covered surfaces of TiO 2 −SiO 2 and SiO 2 supports with uniform small Ru nanoparticles generated in situ. The Ru-TSdc nanocatalyst displayed several interesting promising nanoscale features for hydrogenation of furfural: (i) uniform distribution of Ru, Ti, and Si elements over the entire catalyst surface, (ii) deposition of small Ru nanoparticles with no significant particle agglomeration, (iii) facilitated hydrogen spillover from Ru NPs to the TiO 2 support, and (iv) a significant amount of oxygen vacancies at the nanoparticle surface. For these reasons, the Ru-TSdc sample afforded the optimal performance toward the selective hydrogenation of furfural (up to 99% of selectivity), maintaining good conversions in certain reaction conditions. This work demonstrates how the catalytic activity of metallic nanoparticles could be improved by the structural addition of a reducible oxide, leading to more efficient inorganic supports and for preparing nanocatalysts.