The results from CCD indicated that a quadratic model was appropriate to fit the experimental data (p < 0.0001) and maximum degradation of 95.01 % was predicted at pH = 10, persulfate concentration = 4 mM, initial tetracycline concentration = 30.05 mg/L, and reaction time = 119.99 min. Analysis of response surface plots revealed a significant positive effect of pH, persulfate concentration and reaction time, a negative effect of tetracycline concentration. The degradation process followed the pseudo-first-order kinetic. The activation energy value of 32.01 kJ/mol was obtained for US/S2O82- process. Under the optimum condition, the removal efficiency of COD and TOC reached to 72.8 % and 59.7 %, respectively. The changes of UV–Vis spectra during the process was investigated. The possible degradation pathway of tetracycline based on loses of N-methyl, hydroxyl, and amino groups was proposed.