To study the effects of the support morphology on the hydrodesulfurization (HDS) activity of NiMoS catalysts, ordered mesoporous SiO2 (KIT-6) and nonporous nanospheres of SiO2 were used as supports. Metal species (Ni and Mo) were incorporated through a sequential impregnation technique. The aqueous solution of nickel nitrate was introduced first on the supports, followed by the solution of ammonium molybdate. Subsequently, a sulfidation treatment was carried out in gaseous H2S/H2 atmosphere. The NiMo/Al2O3 commercial catalyst was used as reference. The materials obtained were characterized by N2 physisorption, X-ray diffraction (XRD), and high-resolution transmission electron microscopy (HRTEM) and evaluated in the HDS catalytic reaction of dibenzothiophene in a batch reactor. The results indicate that the textural properties of KIT-6 were the key factors to obtain disperse NiMoS stacks, and a better metal sulfidation, which lead to a higher catalytic activity of the NiMo/KIT-6 catalyst (twice as active) compared to the NiMo/Nanosilica catalyst. In addition, the activity of the NiMo/KIT-6 catalyst was also superior to that obtained for the commercial catalyst.