A Ni-based nanoparticle catalyst was synthesized over a silica support via wet impregnation using either ethylene glycol or water. X-ray diffraction and transmission electron microscopy analysis showed that the particle size of the Ni catalyst prepared using ethylene glycol as the solvent tended to be smaller than that obtained when water was used. The resulting catalysts were tested for performance toward partial oxidation (POX) of isooctane at high weight hourly space velocities (WHSV). The results were compared with those from a Rh-based catalyst, which is commonly used for the same reaction. At a WHSV of 13.8 h(-1), a Ni/SiO2 catalyst with an average Ni particle size of 6.8 nm exhibits higher catalytic activity and stability with an improved resistance to carbon formation than a Ni/SiO2 catalyst with an average Ni particle size of 16.6 nm. The catalyst with the smaller Ni particles outperformed the supported Rh catalyst for the POX of isooctane. To further improve the Ni dispersion and enhance its ability to run at even higher WHSVs with milliseconds of residence time, ceria was used as a promoter. The ceria-promoted Ni catalyst was also prepared by the wet impregnation method using ethylene glycol as the solvent. The addition of ceria corresponded with a further reduction in the size of the Ni nanoparticles and improved Ni dispersion. Using the Ni-Ce/SiO2 catalyst the WHSV could be increased up to 20.0h(-1) while still maintaining its good catalytic activity. At this high WHSV of 20.0 h(-1), the Ni/SiO2 catalyst without the ceria promoter and the Rh catalyst showed severe deactivation due to the formation of surface carbon deposits.