The appearance of large amounts of antibiotics in drinking water and wastewater treatment plants has attracted extensive interest because of the potential resultant environmental and biological risks. Although the Fe(II)/peroxymonosulfate (PMS) system provides a feasible method for antibiotic degradation, the narrow pH range in which it operates and the resultant iron precipitation limit its use. In this study, protocatechuic acid (PCA) was introduced into the Fe(II)/PMS system to improve the system performance. Ciprofloxacin (CIP) was used as the probe reagent. Compared with the Fe(II)/PMS system, the Fe(II)/PCA/PMS system performed better for CIP degradation. This enhanced degradation was attributed mainly to the reduction and chelating ability of the PCA, which enhanced radical generation by accelerating the transformation from Fe(III) to Fe(II) and by forming the PCA-Fe chelate. The Fe(II)/PCA/PMS system also showed a superior degradation ability, even under alkaline conditions, because the PCA-Fe chelate protected iron from precipitation and released hydrogen ions continuously in the process. The electron paramagnetic resonance and alcohol-quenching tests indicated that sulfate and hydroxyl radicals existed in this system and two main CIP degradation pathways were proposed from the liquid chromatography-mass spectrometry results. This work aims to provide new ideas for refractory organics treatment.