The solubility of pyridoxal 5-phosphate monohydrate (PLP) in four binary mixed solvents (methanol + water, ethanol + water, isopropanol + water, and acetone + water) with various compositions were determined at the temperature from 278.15K to 318.15K by the isothermal dissolution equilibrium method under normal atmospheric pressure. The solubility of PLP increased with the increasing temperature and mole fraction of water for the binary mixed solvents ethanol + water, isopropanol + water, and acetone + water. For methanol + water, the mole fraction solubility increased with the temperature at a certain solvent composition, yet the solubility had a maximum value around the mole fraction of water f(c) = 0.8 when the temperature was higher than 308.15 K. The experimental solubility was correlated with the Wilson model, NRTL model, Apelblat equation, and lambda h equation, and the largest value of RMSD was 16.6649 x 10(-5). The Apelblat equation could best describe the solubility behavior according to the result of AIC analysis. Delta G(mix), Delta H-mix, and Delta S-mix, in the mixed solutions were calculated. The dissolution process of PLP in the mixed solvents was spontaneous.