Trends in hydrodesulfurization (HDS) activity are investigated on the basis of surface properties calculated by density functional theory for a series of HDS catalysts. It is shown that approximately linear correlations exist between HS group binding energies and activation barriers of key elementary reactions in HDS of thiophene. These linear correlations are used to develop a simple kinetic model, which qualitatively describes experimental trends in activity. The kinetic model identifies the HS-binding energy as a descriptor of HDS activity. This insight contributes to understanding the effect of promotion and structure–activity relationships.