Four liquid mixtures formed by mixing water and four organic solvents (methanol, ethanol, ethylene glycol, and N,N-dimethylformamide (DMF)) in different ratios were used as solvents, and fenbendazole was used as a solute. The concentration of the solute within T = 283.15-328.15 K and in different mixed solvents was determined by static techniques at p = 101.1 kPa. The experimental solubility of fenbendazole was obviously affected by the solution system temperature and organic solvent concentration. High temperature and high concentration were beneficial to the dissolution of solutes. Conversely, low temperature and low concentration hinder dissolution. In all mixture systems studied, the control of temperature and organic solvent concentration remained unchanged, and the DMF + water system was most beneficial for the dissolution of solutes. Solid powder at the bottom of the vessel when the fenbendazole dispersion process achieved dynamic equilibrium was tested by XPRD. Several thermodynamic cosolvency models Jouyban-Acree model, van't Hoff-Jouyban-Acree model, and Apelblat-Jouyban-Acree model were employed to calculate the solubility data of fenbendazole. The calculation result has a very little error with the experimental value and the relative average deviation value of <= 2.90% and the root-mean-square deviation value of <= 1.440 x 10(-3). The purpose of this work is to provide basic information and extend the library of solubility of bioactive drug fenbendazole in aqueous solutions, relevant for pharmaceutical separation, purification, and further application.