The structure of MoS2/Al2O3 catalyst and the initial step of the hydrodesulfurization (HDS) reaction using an experimental model have been studied by in situ Raman-, infrared emission (IRE)-, inelastic electron tunneling (IET)-spectroscopy and thermal desorption measurements accompanied by molecular modeling and EH-MO calculations. The results show that the catalyst consists of MoS2-like crystallites which are linked via Mo¿O¿Al bonds [d(Mo¿O) ca. 185 pm, angle Mo¿O¿Al ca. 140°] almost perpendicular (but slightly inclined) to the surface of ¿-Al2O3. A pretreatment of the surface of the MoS2 crystallites with hydrogen is mandatory to remove all kinds of S2 groups and to form active (formally) MoII centers at the edge positions. Thiophene, acting as a Lewis acid only towards such centers, is destabilized upon coordination and becomes susceptible for further reaction with hydrogen which may follow, in principle, within the first steps of the route of a Birch reduction.