Adsorption and desulfurization of thiophene on Pt(1 1 0) are investigated using self-consistent periodic density functional theory (DFT), and the reaction network is mapped out for elaborating the possible desulfurization processes. Thiophene has two types of adsorption geometries on Pt(1 1 0), Upright and Flat adsorptions. The S atom inclines to sp3 nonequivalent hybridization in all the adsorption structures of thiophene, whereas the C atom alters between sp2 and sp3 hybridization determined by the interaction modes between the adsorbate and the surface Pt atoms. The extent of molecular distortion of thiophene on Pt(1 1 0) is correlated to the HOMO–LUMO gap of the molecule and the interaction with the surface. Thermodynamic and kinetic analysis of the elementary steps suggest that direct desulfurization pathway is most favorable for the hydrodesulfurization of thiophene on Pt(1 1 0). This desulfurization process exhibits lower CS bond activation energy but higher conversion barrier compared to the situation of thiophene on Pt(1 1 1).