This work describes an efficient novel method to incorporate reactive disulfide bonds onto a silica surface under mild reaction conditions. The reactive thiol groups introduced onto the silicon surface in the first reaction step will be oxidized but easily converted into highly reactive thiopyridyl groups, which can therefore easily be utilized for further organic synthesis involving thiol-containing molecules. This is done in a way that yields approximately a monolayer of reactant on the surface, thereby not adding to the roughness of the surface, of special importance, for instance, for single molecule interaction studies.