The protonation constants of 5,10,15,20-tetrakis(4-sulfonatophenyl)porphyrin, H2tpps4−, were determined in water–ethanol and water–methanol mixed solvents, using a combination of spectrophotometric and potentiometric methods at 20 °C and 0.1 mol⋅dm−3 sodium perchlorate as supporting electrolyte. Two protonation constants, K 1 and K 2, were characterized and were analyzed in various media in terms of the Kamlet, Abboud and Taft (KAT) parameters. Single-parameter correlations of the protonation constant K 1 versus α (hydrogen-bond donor acidity) and π * (dipolarity/polarizability) are poor in all solutions, but dual-parameter (α and π *) correlation represents a significant improvement with regard to the single- and multi-parameter models. However, the single-parameter correlation of log 10 K 2 in terms of β (hydrogen-bond acceptor basicity) shows a better result than dual- and multi-parameter correlations. Linear correlation is observed when the experimental log 10 K 1 and log 10 K 2 values are plotted versus the calculated ones when the KAT parameters are considered. To evaluate the protonation constants of H2tpps4−, the Yasuda-Shedlovsky extrapolation is used to obtain the log 10 K 1 and log 10 K 2 values at zero percent organic solvent. Finally, the results are discussed in terms of the effect of the solvent on protonation.