The molar solubility of bucladesine sodium in water?acetone mixed solvent was measured by High Performance Liquid Chromatography (HPLC) at atmospheric pressure and temperature of 278.15?298.15 K. Moreover, the modified Apelblat, λh and C/R?K models were used to correlate and analyze the experimental solubility data of bucladesine sodium. The thermodynamic properties of bucladesine sodium dissolution process, including the changes of enthalpy, entropy and Gibbs free energy, were calculated based on modified Apelblat model. Furthermore, the molar solubility difference between bucladesine sodium and two related impurities (sodium N6-butyryladenosine-3',5'-cyclic phosphate and sodium 2′-O-butyryladenosine-3',5'-cyclic phosphate) in mixed solvent was determined as the molar fraction of acetone was 0.7110～1.0000. The results showed that the molar solubility of bucladesine sodium in mixed solvent increased as the temperature increased. With increasing molar fraction of acetone, the molar solubility of bucladesine sodium increased to the maximum and then decreased, which could be explained by cosolvent phenomenon. When the molar fraction of acetone was 0.4220, the molar solubility of bucladesine sodium was the largest. It was found that the three models showed good correlation effect with low relative average deviation (RAD) and root-mean-square deviation (RMSD) values which demonstrated that the correlated values were in good agreement with the experimental values throughout the entire range of temperature and tested molar fraction of acetone. The change of enthalpy of dissolution process was positive while the change of Gibbs free energy was negative, which indicated that the dissolution process of bucladesine sodium in mixed solvent was a spontaneous endothermic process. The molar solubilities of bucladesine sodium and two related impurities increased with increasing temperature and decreased with increasing molar fraction of acetone, but there was a significant difference between the molar solubility of bucladesine sodium and two related impurities as the molar fraction of acetone increased from 0.7110 to 0.8538. The above solubility characteristics of bucladesine sodium and two related impurities could be used as the basic data for further study in bucladesine sodium crystallization process.