Abstract: The thermodynamic functions of protonation reactions of phenylalanine, leucine, tryptophan and methionine have been determined by titration calorimetry combined with computer fit program for thermodynamic function and it has been reported that there are differences between ΔH, logβ, ΔG and ΔS of protonation reactions of amino acids. From the experimental results, the differences are related to the nature of the side chain substituent group R of asymmetric carbon atom of α-amino acid and the sequence of the differences has also been reported.