Size effect on thermodynamics and diffusion of deuterium in nano-sized vanadium (V) layers is studied. Critical temperature (T-c) for deuterium phase transition is found to decrease with the inverse thickness of V layers and the thermodynamic factor increases as V thickness decreases. These effects are related to the deuterium-deuterium (D-D) interaction change versus V thickness, which experimentally proves that the D-D interaction plays the main contribution to the previously observed V size effect on deuterium chemical diffusion coefficients (D-c). The self-diffusion coefficients (D-s) are obtained through correcting D-c with the thermodynamic factors. It is found that the D-s are similar in 14 and 28 monolayers of V while slightly larger D-s are observed at high concentrations in 14 atomic layers. The weak site blocking effect in the interface is argued to be the main contribution to the observed size effect on D-s.