Ru/CNF catalysts of different Ru nanoparticle (NP) sizes (0.9-2.7 nm) were assessed for their performance in continuous supercritical water gasification (SCWG) of glycerol. A structure sensitivity of Ru was demonstrated, with high initial turnover frequencies (TOF) for Ru NPs smaller than 1.2 nm. Deactivation happens essentially through: 1) coking, which occurs more readily at low Ru surface densities and is limited to nanometric layers, and 2) sintering, which led to final NP sizes ranging from 2 to 3 nm independent of the catalyst loading (1 to 30 wt% Ru). A correlation between TOF and the density of surface Ru atoms was found, with an optimal surface density (0.4-0.7 atomRu,sfc nm−2) resulting in high initial and good steady-state TOFs, allowing longer lifetimes through the delay of coke formation. CNF as a support enables high metal loadings with optimal performance, which could help in decreasing the volume of high-pressure vessels and hence the cost of SCWG plants, making this technology even more attractive.