The degradation of anthraquinone dye Reactive Blue 19 by using O3 and O3 / S2O8 2- in the advanced oxidation processes is studied to investigate the performance of these two systems. The response surface method with a Box-behnken Design was successfully applied to identify the relationship between operating variables such as initial concentration, S2O8 2- dosage and contact time in order to determine the optimum operating condition. The quadratic model for the percentage COD removal (response) proved to be significant for the degradation of the dye. The COD removal efficiency under Box-behnken Design and experimental test were found to be 96.2% and 83.9% under the optimum conditions. Furthermore, the result obtained showed that the O3 / S2O8 2- system is more effective than the O3 only in treating the Reactive Blue 19.