Results are reported on the support effect on the catalytic activity in thiophene hydrodesulfurization (HDS) of sulfided Ni-Mo catalysts supported on pure niobia, mixed oxides of Nb 2 O 5 -TiO 2 prepared by sol-gel method, and Nb 2 O 5 /TiO 2 and Nb 2 O 5 /Al 2 O 3 prepared by surface deposition. The prepared samples were characterized using N 2 adsorption at 196 ı C, X-ray diffraction (XRD), and temperatureprogrammed reduction (TPR) techniques. This study showed activity variation as a function of support composition. The activity of niobia-rich catalysts was no longer promoted by the synergy between Ni and Mo. The absence of synergy between molybdenum and nickel on niobia can be explained by the strong interaction of each metal with niobia at the expense of interaction with each other. It was found that 5 wt% Nb 2 O 5 /TiO 2 -supported catalyst was the better catalyst for thiophene HDS. It was shown that by means of an adequate support design it is possible to significantly increase the functionalities of HDS catalysts. Semiconducting supports like TiO 2 can improve the HDS activity by exerting electronic effects on the active phase, helping in this way the formation of sulfur vacancies. The 5 wt% Nb 2 O 5 /TiO 2 was also tested at high pressure with gas oil feedstock. It is observed with the hydrogeolysis of sulfur compounds against time-on-stream that the activity of this catalyst decreases fast with time.