Protocatechuic acid (PA) is a natural phenolic compound which has been proven to have chemopreventive property against chemically induced carcinogenesis. The mixing enthalpies of PA with N-glycylglycine in sodium phosphate and potassium phosphate buffer solutions with different pH values have been investigated by mixing-flow isothermal microcalorimetry at T = 298.15 K. The heterotactic enthalpic interaction coefficients (h(xy)) in the pH range of phosphate buffer solution from 3.0 to 8.0 have been calculated according to the McMillan-Mayer theory. Trends of the enthalpic pairwise interaction coefficients (h(xy)) with increasing pH in both phosphate buffer solutions were obtained. The solvent and pH dependence of the h(xy) were discussed in terms of molecular interactions between solvated solute molecules.