The relative hydrodesulfurization reactivities of heterocyclic sulfur compounds collected from our experiments and the literature were correlated with their electronic parameters estimated using MOPAC-PM3. It is found that the direct hydrogenolytic S elimination (direct hydrogenolysis) of sulfur-containing compounds is definitely Correlated with the electron density of their S atoms, while the hydrogenation of the thiophenic ring or neighboring ring prior to hydrogenolysis correlated with the bond order of the most unsaturated bond in the ring. Methyl groups at 4- and/or 6-positions of dibenzothiophene may sterically retard direct hydrogenolysis. Hence, the hydrogenation of the aromatic ring adjacent to the thiophenic ring followed by the hydrogenolysis is a major route for such species. The molecular orbital calculation clarified that the hydrogenation of refractory sulfur compounds with alkyl steric hindrance accelerates their hydrogenolysis by reducing the steric hindrance through molecular puckering and by increasing the electron density on S. The calculation allows us to estimate reactivities of sulfur-containing compounds in both routes and to design the reaction scheme to ensure the most efficient hydrodesulfurization.