The effect of the preparation method of CoMo/SiO2 catalysts with and without sodium ions, on the hydrodesulfurization (HDS) of thiophene was investigated by X-ray diffraction (XRD), X-ray photoelectron spectroscopy (XPS) and N-2 physisorption (BET). The samples were prepared by total sol-gel route, by classic wetness impregnation and by co-impregnation, in the presence of nitrilotri acetic acid (NTA), of commercial and sol-gel prepared silica. The influence of sodium ions added to the sol mixture and to the silica before the impregnation with Co and Mo salt solution, was also considered. The presence of sodium favoured the phase transition of amorphous silica to cristobalite with consequent reduction of the surface area and of the catalytic activity. The catalysts prepared by the sol-gel method exhibited better metal oxide dispersion but lower catalytic activity. On the contrary the catalysts supported on home-made sol-gel silica were quite active in spite of the lower surface areas and the low metal dispersion. Addition of NTA to the impregnation solution yielded better performing catalysts.