The Fenton-like degradation of nalidixic acid was studied in this work. The effects of Fe(3+) concentration and initial H(2)O(2) concentration were investigated. Increasing the initial H(2)O(2) concentration enhances the degradation and mineralization efficiency for nalidixic acid, while Fe(3+) shows an optimal concentration of 0.25 mM. A complete removal of nalidixic acid and a TOC removal of 28 % were achieved in 60 min under a reaction condition of [Fe(3+)] =0.25 mM, [H(2)O(2)] =10 mM, T=35 °C, and pH=3. LC-MS analysis technique was used to analyze the possible degradation intermediates. The degradation pathways of nalidixic acid were proposed according to the identified intermediates and the electron density distribution of nalidixic acid. The Fenton-like degradation reaction of nalidixic acid mainly begins with the electrophilic attack of hydroxyl radical towards the C3 position which results in the ring-opening reaction; meanwhile, hydroxyl radical attacking to the branched alkyl groups of nalidixic acid leads to the oxidation at the branched alkyl groups.