In order to develop a fundamental understanding of the HDS mechanism of thiophenic compounds over molybdenum disulfide (MoS2), a molecular simulation of the hydrodesulfurization (HDS) of thiophenic compounds over MoS2 has been performed using Zerner's Intermediate Neglect of Differential Overlap (ZINDO) program. On the basis of the calculated edge structure, stoichiometry of MoS2, shape of the crystal, and the size corresponding to real MoS2 particles, a single-slab cluster, Mo27S54, has been proposed for modeling the highly dispersed MoS2. The proposed cluster is a regular hexagon with ((1) over bar 010) and (30 (3) over bar 0) edge planes only. According to the calculated electronic properties of the surface, the coordinately unsaturated Mo-IV in the (30 (3) over bar 0) plane is expected to be the active site for hydrogenation of thiophenic and aromatic compounds. The most stable adsorption configuration of thiophene on the Mo-IV is a flat adsorption configuration via the eta(5)-bound coordination, whereas the most stable adsorption configuration of tetrahydrothiophene (THT) on the Mo-IV is a tilted adsorption configuration via the S-bound coordination. HDS mechanism of thiophene through the hydrogenation pathway over the (30 (3) over bar 0) plane of MoS2 is discussed according to quantum chemical insights in combination with experimental results from the literature.