The photo-oxidation of water on the rutile TiO2 (110) surface is investigated using density functional theory calculations. A stable (TiO2)26 cluster is used to model the rutile bulk and (110) surface. A model in which every reactant state contains a photoinduced positively charged cluster and every product state contains a neutral cluster plus a proton is used to study the photo-oxidation of water. In each reaction step, a photoinduced hole localized in the surface reacts with an adsorbed atom or molecule surrounded by water leading to a neutral cluster, a proton surrounded by water, and a product vacancy, adsorbed atom, or molecule. According to this model the illumination of the TiO2 (110) surface with light provides enough overpotential for the photo-oxidation to proceed spontaneously.