Experimental and theoretical studies of hydrodeoxygenation (HDO) of m-cresol show that on metals of low oxophilicity, such as Pt or Pd, the direct C-O bond cleavage is not possible. Therefore, HDO requires an indirect pathway via tautomerization. In contrast, on metals of higher oxophilicity, such as Ru or Rh, the direct C-O bond cleavage is possible and toluene can be directly obtained from m-cresol. These studies show that the HDO activity correlates directly with the metal oxophilicity, which in turn depends on the position of the d-band center relative to the Fermi level. This catalytic descriptor depends on (1) the type of metal and (2) the extent of coordination of the metal atoms. The present contribution investigates the effect of the second factor. It is demonstrated that a Rh/SiO₂ catalyst with small particles (low-coordination sites) is more active for HDO than one with larger particles (high-coordination sites). At the same time, the low coordination site is more prone to deactivation and loss of HDO selectivity. These experimental results are combined with the density functional theory calculations, which show that the energy barrier for direct C-O bond cleavage is lower on a step site than on a terrace site. At the same time, it is shown that a step site requires a higher energy barrier to remove adsorbed molecular fragments to regenerate the activity than a terrace site, which explains the faster deactivation rate observed on catalysts with small more defective metal clusters.