Dissolution of nanoparticles is involved in the preparation, research and application of nanomaterials, but there is a surprising difference in dissolution thermodynamics between nanoparticles and the corresponding bulk materials. In the paper, the relations of dissolution thermodynamic properties, equilibrium constant of nanoparticles, respectively, and particle size were derived by introducing interface variables and the surface chemical potential. Experimentally, the solubility of nano-barium sulfate with different average particle sizes at different temperatures were determined by the method of electrical conductivity, obtaining the influencing regularities of particle size on the dissolution thermodynamic properties and the equilibrium constant. The regularities are in accordance with the theory. The results show that there are remarkable effects of particle size of nanoparticles on the dissolution thermodynamic properties and the equilibrium constant; with the decreasing of the size of nanoparticles, the dissolution equilibrium constant increases, while the standard dissolution Gibbs free energy, the standard dissolution enthalpy and the standard dissolution entropy decrease; and the logarithm of the dissolution equilibrium constant, the standard dissolution Gibbs free energy, the standard dissolution enthalpy and the standard dissolution entropy are linearly associated with the reciprocal of particle size, respectively. This new theory provides a quantitative description of nanoparticles dissolution behavior, and has important scientific significance for understanding and predicting of thermodynamic regularity of dissolution concerned in the preparation, researches and applications of nanomaterials.