The kinetics of the photocatalytic degradation reactions of twelve ortho/para mono-substituted phenols containing electron-donating or -withdrawing groups have been investigated experimentally. With the intention of determining the most suitable DFT reactivity descriptors, geometry optimizations of the compounds have been performed with the Density Functional Theory DFT at B3LYP/6-31G* level. In order to take the effect of solvent water into account, the calculations have been repeated for the optimized structures by using COSMO as the solvation model. Chemical hardness, softness, electronegativities, Fukui functions, local hardness and softness, local electrophilicities and softness differences for all phenol molecules have been calculated. Correlations between the apparent initial first-order rate constants determined in the experiments and the calculated DFIP reactivity descriptors have been examined. Results show that the reactions investigated are electrophilic in nature. The local softness and softness differences correlate well with the reaction rates indicating that soft-soft interactions dominate in the photocatalytic degradation reactions of phenols.