Hydrodesulfurization (HDS) of thiophenic sulfur with hindered groups in the presence of inhibitors (nitrogen compounds and H2S) is vital in achieving ultralow sulfur level in gasoline. The objective of this research was to investigate effects of inhibitors and hindered groups on ultra-deep HDS of thiophenic sulfur on Ni2P catalyst in a mechanistic perspective. Density functional calculations were used to investigate adsorption of inhibitors and sulfur compounds combined with thermodynamic analysis. Activation mechanism of sulfur compounds was studied using partial density of state (PDOS) and electron density difference analysis. All species preferred to be adsorbed at the three-fold hollow Ni site and its vicinity. Inhibitors had larger adsorption energy and constant than sulfur compounds. Co-adsorption of thiophene and inhibitors weakened the adsorption of thiophene. Population analysis revealed that some electrons moved to higher energy states suggesting activation. Sulfur compounds adsorbed to Ni2P surface mainly through Ni-S bonds exhibiting characteristics of covalent bonding, originating from the overlapping of 3p states of S and 3d states of Ni. Inhibitors show tendencies to adsorb to Ni2P surface over sulfur compounds. Hindered groups impede adsorption of sulfur compounds and weaken the interaction between sulfur compounds and surface mainly due to steric hinderance.