Multiparameter regression analysis combined with the principle of linear correlation of solvation energies was applied to assess the solvent effect on the acidity of the lignin-related phenols in water-acetone systems. The coefficients a, b, and s of the Kamlet-Taft equation were calculated taking into account the contributions of different types of solute-solvent interactions to the protolytic properties of the phenols of the guaiacol series.