The solubility of diphenhydramine hydrochloride (DH) in four pure solvents (methanol, ethanol, acetone and ethyl acetate) and two binary solvents (ethanol + ethyl acetate) and (ethanol + acetone) was determined at temperatures from (278.15 to 323.15) K. The experimental solubility of DH is well correlated by the modified Apelblat equation, the CNIBS/R-K equation and the hybrid model, respectively. All the measured solubility of DH shows temperature dependence, In binary mixtures, the solubility curve displays a maximum with the solvent composition changing, particularly, the maximum point increases with temperature. Moreover, the activity coefficients as well as thermodynamic properties of mixing were obtained and discussed. (C) 2015 Elsevier Ltd. All rights reserved.