Hydrodesulfurization (HDS) of sour crude oil is an effective way to address the corrosion problems in refineries, and is an economic way to process sour crude oil in an existing refinery built for sweet oil. In the current study, the HDS of Siberian crude oil was carried out in a slurry reactor. The Co-Mo, Ni-Mo, and Ni-W catalysts sup-ported on γ-Al2O3 were compared at the temperature of 340 ℃ and the pressure of 4.5 MPa. The HDS activity fol-lows the order of Co-Mo>Ni-Mo>Ni-W at a high concentration of H2S, and the difference between Co-Mo and Ni-Mo becomes insignificant at a low concentration of H2S. The influence of reaction temperature 320-360 ℃ and reaction pressure 3-5.5 MPa was investigated, and both play a positive role in the HDS reaction. A kinetic model over Ni-Mo/Al2O3 in the slurry reactor was established. The activation energy is estimated as 60.34 kJ·mol-1;the orders of sulfur components and hydrogen partial pressure are 1.43 and 1.30, respectively. The kinetic parameters are compared with those in a trickle-bed reactor, implying that the mass transfer is greatly enhanced in the slurry reactor. The back mixing effect is present in the slurry reactor and can be reduced by a multi-stage design, which would lead to higher reactor efficiency in industrial application.