To explore the origin of the enhanced photocatalytic activity of Mo-doped monoclinic BiVO4, variations of the structures and the electronic properties, as well as the adsorption behavior of water on the (010) surface, introduced by the Mo dopant have been investigated by means of density functional theory computations. For the bulk phase, Mo atoms prefer to substitute the V atoms, which can effectively accelerate the separation of carriers. For the (010) surface, Mo atoms prefer to substitute the Bi atoms at the outermost layer. Mo doping on the surface can result in surface oxygen quasi-vacancies and enhance the exposure of surface Bi atoms, which is confirmed to improve the adsorption of water molecules. Our results demonstrate that the enhanced photocatalytic activity of Mo-doped monoclinic BiVO4 is derived from the facilitated separation of photoinduced carriers and introduced surface oxygen quasi-vacancies.