In the present study, the electrochemical oxidation of 22 phenolic compounds was systemically examined at the RuO2-SnO2-Sb2O5 electrode to elucidate the inherent structure-reactivity correlation. The oxidation process was monitored in situ by UV-vis spectroscopy. A variety of substituents (e.g., -CH3, -NH2, -Cl, -OH, -COOH, -NO2, -CHO) were employed in order to cover various possible electronic effects. Our experimental results revealed that the relationship between the Hammett constant and rate constant for the electrochemical oxidation of phenolic compounds at the RuO2-SnO2-Sb2O5 electrode was different from the results obtained at a platinum electrode. The substituted phenols with electron-withdrawing groups were electrochemically oxidized more rapidly than those with electron-donating groups. To decipher the effects of physiochemical properties on the electrochemical reactivity of phenolic compounds, 140 molecular descriptors were calculated and assessed for each phenolic compound; a quantitative structure property relationship (QSPR) model was developed. Correlations between the rate constants and quantum properties of the phenolic compounds were achieved using partial least-squares (PLS) analysis. The most crucial quantum descriptors responsible for the electrochemical reactivity of phenolic compounds were determined to be E-HOMO, chemical potential, total dipole, quadrupoles, subgraph counts, relative positive charged surface area, and pK(a). The proposed QSPR model was based on the quantum descriptors derived from the whole molecule, providing lucid explanation and effective prediction of the electrochemical reactivity of various phenolic compounds.