Thiophenes are the major sulfur compounds contained in transportation fuels, and the removal of thiophenes dictates the degree of deep desulfurization of fuels. A new desulfurization method is presented in the present work, and its effectiveness was proved with a model fuel composed of 80 wt % n-octane, 20 wt % benzene, and 2000 ppmw thiophene. Formaldehyde and HCl were preloaded in the pore spaces of silica gel, and a condensation reaction with thiophene occurred. The reaction product was also adsorbed in the pores. The effects of different structural properties of silica gel, loading amount of the reactant and catalyst, temperature, and other factors on the desulfurization performance were studied. It was shown that all thiophene contained in the fuel can be effectively removed with a reasonable reaction rate at a moderate condition irrespective of the existence of aromatic components or moisture in the fuel.