Abstract This paper evaluated the COD, TOC removal and molecular frontier energies in the ozonation of naphthalene sulfonic acids (NSAs). It was found that both COD and TOC degradation of the 11 compounds followed the pseudo-first-order kinetic and the reaction rate constants with ozone varied widely. A linear relationship between logarithm of global COD degradation rate constant and the energy of the highest occupied molecular orbit, E homo, was obtained for these NSAs with a regression coefficient of 0.88 and a slope of 0.4672 eV −1. TOC degradation kinetics also reached similar results with a regression coefficient of 0.90 and a slope of 0.9336 eV −1. The results of correlation analysis suggested that TOC and COD removal in ozonation of NSAs follow the frontier orbital theory and can be predicted by E homo, which indicated that electrophilic effect was the main factor in the ozonation of NSAs. Therefore, it is possible to improve the biodegradability of dyestuff wastewater bearing mainly NSAs by ozonation at an accepted cost and evaluate the economy of ozonation process.