The reactivity of phenolic compounds can be drastically affected by the electronic nature of substituents and by their positions in the aromatic ring. In this work, structure effect on the photoreactivity via TiO2 catalysis is studied using several substituted phenols in order to cover a wide variety of electronic effects, ranging from strong electron-donating (activating) to strong electron-withdrawing (deactivating) groups: ---OH, ---OCH3, ---OCH2CH2CH3, ---COOH, ---COH, ---COCH3, ---NO2, ---SO3H, ---CN, ---CF3, ---F, ---Cl, ---Br, and ---I. Results indicate that the fastest initial degradation rate for substituted phenols occurs for p-methoxyphenol and the slowest for the p-nitrophenol. Quantum chemically derived properties and experimental data for each phenol derivative were used to establish structure–photoreactivity relationships (SPR) for these compounds using regression techniques. According to the statistical calculations, the most critical electronic properties responsible for the photoreactivity of p-substituted phenols were the zero-point energy, the total energy divided by the molecular weight, and the quadrupolar moment for the xy plane. These molecular descriptors encode information related to the molecular vibration frequencies, intra-molecular interactions, and total electron distribution around the molecule, respectively. This SPR approach offer a better explanation of the para-phenols photoreactivity properties than the use of Hammett constant because it considers properties derived from whole molecules whose atoms interact with the light based on the electron density and electronic molecular shape.