The solubility of chlorphenesin (CHP) in 12 solvents was determined by the gravimetric method from 288.15 to 328.15 K under atmospheric pressure. The experimental results were correlated by three thermodynamic models (Apelblat equation, Ah equation, and NRTL model). The average relative deviations (ARDs) in the Apelblat equation and NRTL model were less than 5%, indicating a good correlation with the experimental results. In addition, the mixing thermodynamic properties (Delta H-mix, Delta(mix),G, and Delta S-mix) in 12 solvents were calculated by the NRTL model, in which all the Delta(mix)G values were negative and Delta(mix) S values were positive, indicating that the mixing process is spontaneous. Finally, the solvent physicochemical properties were investigated to visualize the solvent effects on solubility results. The results indicated that the solubility of CHP in alcohol and ester systems was mainly affected by the solvent polarity and viscosity.