ABSTRACT In the treatment of water and wastewater, more emphasis is paid to the advanced oxidation process (AOP) based on (S 2 O 8 2– ) radicals. In this work, the degradation of a toxic dye (Orange G) using the heat-activated persulfate was examined Plackett and Burman designs experiments were used to investigate the effects of several parameters on the oxidation of the OG by K 2 S 2 O 8 , including persulfate concentration K 2 S 2 O 8 , the initial dye concentration, the reaction time, the initial solution pH, and temperature. The screening results identify three more influential factors that are subsequently studied by the response surface methodology employing Box–Behnken design to determine optimal conditions for maximal degradation effectiveness. The estimated values agreed with the experimental data, with a coefficient of the determination R 2 = 0.9429. The forecasted data revealed that with a concentration of Orange G 2 mg/L, a concentration of persulfates of 27.018 mM and a temperature of 45.5°C, a maximum orange degradation of 100% could be attained. The efficacy and the benefits of the advanced oxidation method using heat-activated persulfate for technological and industrial applications for the degradation of the organic pollutants have been well-proven in this work.