Two mesoporous material Ni/γ-Al2O3 catalysts were prepared and characterized by ICP-AES, XRD, and TPR. The differences in reaction activity between Ni-in-Al2O3 and Ni-on-Al2O3 were investigated for hydrotreating of crude 2-ethylhexanol. The results show that the Ni species (Ni-on-Al2O3) exhibit excellent hydrogenation activities at a wide range of H2 pressure and space velocity, while the Ni species (Ni-in-Al2O3) exhibit similar activities with those of Ni-on-Al2O3 only at higher H2 pressure and lower space velocity. Due to the presence of extensively exposed Ni species on the Ni-on-Al2O3 catalyst, its hydrogenation performance was increased significantly because of the low interphase mass transfer resistance.