Abstract: A variety of TiO₂-Al₂O₃ composite support were prepared using improved sol-gel method (SG), co-precipitation method (CP), surface precipitation (PR) and mechanical kneading method (ME), and the influence of preparation methods on their physical properties were investigated. The hydro-desulfurization activity of Co-Mo/TiO₂-Al₂O₃-X catalysts prepared by impregnation method was studied. XRD, BET and SEM were used to characterize the composite support and the catalysts. Results show that the composite support prepared by SG method has uniform morphology with larger surface area, pore size and pore volume. And the monolayer or sub-monolayer of TiO₂ existed in the γ-Al₂O₃. Under the reaction conditions of 3.0 MPa of hydrogen pressure, 280℃ of reaction temperature, 4 h of reaction time, 1.4 h^-1 of the liquid space velocity and 600 of hydrogen to oil ratio, Co-Mo/TiO₂-Al₂O₃ prepared by SG method has highest hydro-desulfurization activity, and the thiophene conversion rate reached 96.6%.