The equilibrium solubility of sulfenone in various aqueous cosolvent systems was determined by isothermal saturation method at 278.15–323.15 K under 101.2 kPa. Four cosolvents (methanol, ethanol, isopropanol and n-propanol) exhibited different power in dissolving. The specific performance was that in the saturated state, the content of sulfenone in n-propanol + water was the most and in methanol + water was the least. The Jouyban-Acree (J-A), van’t Hoff-Jouyban-Acree (V-J-A) and Apelblat-Jouyban-Acree (A-J-A) models were utilized to correlate the obtained solubility data of sulfenone. The maximum of relative average deviation (RAD) and root-mean-square deviation (RMSD) were 1.47 × 10−2 (from A-J-A) and 6.07 × 10−5 (from V-J-A). In addition, the difference in dissolution was explained from a microscopic point of view through the acquisition of hansen solubility parameters (HSPs). The preferential solvation parameter δx1,3 was calculated by Inverse Kirkwood-Buff Integrals (IKBI) method, the change trend of δx1,3 presented in the entire concentration range was non-linear. The apparent thermodynamic parameters were calculated by van’t Hoff plots and the results indicated that the dissolution process of sulfenone is an endothermic and entropy increment process.