The aim of this study was to determine the removal of ciprofloxacin (CIP) by the electro-persulfate (EC-PS) process using aluminum (Al) electrodes. The effects of variables including pH, contact time, PS concentration, initial CIP concentration and current density on the removal efficiency of CIP were studied. In order to determine the mechanisms of the EC-PS process, the radical scavenger tests, as well as EDS and FT-IR spectroscopy were performed on the sludge. The results showed that the PS process alone had no effect on the CIP removal, and the EC process alone could remove 25% of CIP after 160 min. However, the EC-PS process under the optimum conditions: pH of 7, time of 40 min, current density of 2.75 mA/cm2, CIP concentration of 20 mg/L, and PS concentration of 0.84 mM removed 90% of CIP. The effect of the EC-PS process on the actual hospital wastewater was 81% in optimal conditions. The kinetic study also showed that the second-order kinetic model was the most consistent. The oxidation process during the initial contact was dominant in the EC-PS process and, over time, the EC process was dominant for CIP removal.