A series of ceria-supported Fe catalysts with a trace amount of noble-metal modification (NM-Fe/CeO2, NM = Pt, Ir, Pd, Rh, and Ru) were prepared by the co-impregnation method and used for guaiacol hydrodeoxygenation (HDO) to phenolic compounds at 673 K and atmospheric pressure. In the absence of H2O, the addition of noble metal improved the initial activities but showed severer deactivation than Fe/CeO2. Conversely, the addition of water showed little effect on the initial activity and helped to improve the stability of NM-Fe/CeO2. Among all of the tested NM-Fe/CeO2catalysts, Pt-Fe/CeO2showed the highest guaiacol conversion. The X-ray absorption spectroscopy (XAS) characterization confirmed that the original structure of active FeOxspecies, probably Fe4O6, was mostly preserved after the addition of Pt. The Pt modifier was completely reduced to form Pt1Fe4single-atom alloy (Pt1Fe4SAA) clusters during the guaiacol HDO reaction. These Pt1Fe4SAA clusters probably promoted the reduction of FeOxspecies to form the coordinatively unsaturated sites (CUS), which were the active sites for the HDO reaction. The presence of Pt1Fe4SAA clusters also encouraged the dissociation of H2O on Pt-Fe/CeO2to maintain the catalytic activity under the H2O-containing conditions, as shown by the temperature-programmed surface reaction with H2O (H2O-TPSR). Characterization of spent catalysts with Raman spectroscopy, scanning transition electron microscopy (STEM), and XAS showed that the Pt-Fe/CeO2catalyst was deactivated by coke deposition and carburization of Fe4O6clusters in the absence of H2O, while the growth of coke species and the formation of inactive iron carbide were suppressed in the presence of H2O.