Conclusion Sonochemical degradation of TC in the presence of S2O82− was investigated with focusing on the optimizing of the operation parameters such as pH, S2O82− concentration, initial TC concentration and reaction time. This study indicated that RSM was the suitable method to optimizing the best operating conditions to maximizing the TC degradation. The reaction time showed the highest effect on the TC degradation, followed by initial S2O82− concentration, initial TC concentration and pH. Under optimal conditions, the TC degradation rate, COD and TOC removal efficiency were found to be 95.01 %, 72.8 % and 59.7 %, respectively. The degradation process followed the pseudo-first-order kinetics. The activation energy value of 31.71 kJ/mol implies that the degradation of TC by US/S2O82− process is thermodynamically feasible. The ultraviolet visible spectra obtained before and after ultrasound irradiation in the presence of S2O82− indicated that proposed degradation pathway for tetracycline was based on loses of N-methyl, hydroxyl, and amino groups. Overall, US/S2O82− process was found to be a promising technology for TC degradation in aqueous solution.