Removal of tetracycline hydrochloride (TCH) in aqueous solution was conducted by coupling electrolysis with persulfate oxidation, wherein a synergistic effect occurred. Batch tests were performed to investigate the influence of various operation parameters, including current density, persulfate concentration and initial pH. It is remarkable that TCH pollutants could be removed effectively by means of electro-activated persulfate oxidation, in which both hydroxyl and sulfate radicals offer the predominant oxidizing species. The removal efficiency of total organic carbon (TOC) reached 31.3% within 4 h, while up to 43.0% with further prolongation of reaction time to 12 h. In this study, electro-activated persulfate oxidation is verified to be an effective manner for TCH degradation in wastewater.