Diflufenican equilibrium solubilities when dissolved in a series of cosolvent mixtures of (ethanol + water), (ethylene glycol, EG + water), (propylene glycol, PG + water), and (N,N-dimethyl formamide, DMF + water) were determined and analyzed by the isothermal saturation method from 278.15 to 323.15 K at an ambient pressure of 101.2 kPa. Four pure organic solvents including ethanol, EG, PG, and DMF showed great dissolving capacity in various aqueous cosolvency systems and their solubility (in mole fraction) order was as follows: DMF (2.983 x 10(-3), 323.15 K) > PG (2.454 x 10(-4), 323.15 K) > ethanol (1.129 x 10(-4), 323.15 K) > EG (7.490 x 10(-5), 323.15 K) > water (1.042 x 10(-6), 323.15 K). Among many factors, temperature and solvent water content were the two variables that had the greatest impact on diflufenican solubility. Taking temperature as an example, the monotonicity of the drug mole fraction curve was in step with the changing trend of the temperature. On the contrary, the monotonicity of the dissolved amount was in an antagonistic relationship with the trend of the water content of the solvent. It was found that the maximum solubility (2.983 x 10 73 , 323.15 K) was observed in the DMF + water system. X-ray powder diffraction (XPRD) was used to characterize the diflufenican crystal samples to eliminate the possibility of chemical reaction and formation of solvates when diflufenican is mixed with various solvents. Thermodynamic mathematical models (Jouyban-Acree model, Van't Hoff-Jouyban-Acree model, and the modified Apelblat-Jouyban-Acree model) were used to analyze and correlate the equilibrium diflufenican solubilities in the four cosolvent mixtures. The largest RAD and RMSD obtained from the three cosolvency models were 2.83 x 10(-2) and 1.15 x 10(-5) based on the correlation results, respectively. All models provided a good description of the solubility behaviors of diflufenican and the Jouyban-Acree model gave the best fitting results. The entire data obtained in this work are helpful for purification and recrystallization processes.