The enthalpies of dilution of protocatechuic acid, a natural anti-cancer substance, in sodium phosphate and potassium phosphate buffer solutions with different pH values were measured by using a mixing-flow microcalorimeter at T = 298.15 K. Densities of the pseudo binary system (phosphate buffer + protocatechuic acid) were also measured with a quartz vibrating-tube densimeter. The enthalpic interaction coefficients (h(2), h(3) and h(4)) were computed according to the McMillan-Mayer model. Apparent molar volumes of the system were calculated from the data of densities, which have been used to deduce limiting partial molar volumes (V-phi(0)) of protocatechuic acid at different pH values. The aim of the experiments and data process is to investigate the interaction between the molecules of the important drug and that of the drug molecule with coexistent species in aqueous solutions as well as the influences on these interactions of such factors as pH and ion strength. Change trends of the enthalpic pair wise interaction coefficient h(2) and V-phi(0) of protocatechuic acid with pH increasing in the both phosphate buffer solutions were obtained. The thermodynamic properties, h(2) and V-phi(0) in potassium phosphate buffer solutions were compared with those in sodium phosphate buffer solutions at identical pH. The trends and the differences have been discussed in terms of the (solute + solute) and (solute + solvent) interactions. (C) 2014 Elsevier Ltd. All rights reserved.