As the solvent system ethanol + cyclohexane is selected for the purification of clopidogrel hydrogen sulfate (Form II) [CHS(II)], the solubilities of CHS(II) in the binary solvent mixtures were measured at the temperatures ranging from (283.35 to 333.75) K. The solubility increased with both the rising temperature and mole fraction of ethanol in the binary solvent. The experimental data were well-fitted by the Jouyban−Acree model, and the thermodynamic parameters were calculated correspondingly. The result demonstrated that the dissolution process of CHS(II) in the ethanol + cyclohexane mixture was endothermic and entropy-driven.