Mesostructured titania as support for the CoMoS active phase in deep HDS of 4,6-dimethydibenzothiophene leads to a modification of the main desulfurization way in contrast with the conventional CoMoS/alumina catalyst. Indeed, the dispersion of MoS2 active phase onto mesostructured titania supports leads to catalysts, which favor the direct desulfurization of 4,6-dimethydibenzothiophene. We demonstrate that this unexpected behavior is related to the intrinsic acid properties of the supports, arising from the coexistence of amorphous phase with semi-crystalline anatase. Indeed, these solids present both Lewis and Bronsted acidities, which are conserved after the impregnation of cobalt and molybdenum. The characteristic and the efficiency of the mesoporous titania catalysts have been compared either with conventional Al2O3, used for hydrotreatment, or P25, a commercial TiO2 support used as titania reference.