The UV/chlorine process, which forms several reactive species including hydroxyl radicals (HO) and reactive chlorine species (RCS) to degrade contaminants, is being considered to be an advanced oxidation process. This study investigated the kinetics and mechanism of the degradation of trimethoprim (TMP) by the UV/chlorine process. The degradation of TMP was much faster by UV/chlorine compared to UV/H2O2. The degradation followed pseudo first-order kinetics, and the rate constant (k′) increased linearly as the chlorine dosage increased from 20 μM to 200 μM and decreased as pH rose from 6.1 to 8.8. k′ was not affected by chloride and bicarbonate but decreased by 50% in the presence of 1-mg/L NOM. The contribution of RCS, including Cl, Cl2− and ClO, to the degradation removal rate was much higher than that of HO and increased from 67% to 87% with increasing pH from 6.1 to 8.8 under the experimental condition. The increasing contribution of RCS to the degradation with increasing pH was attributable to the increase in the ClO concentration. Kinetic modeling and radical scavenging tests verified that ClO mainly attacked the trimethoxybenzyl moiety of TMP. RCS reacted with TMP much faster than HOCl/OCl− to form chlorinated products (i.e., m/z 325) and chlorinated disinfection byproducts such as chloroform, chloral hydrate, dichloroacetonitrile and trichloronitromethane. The hydroxylation and demethylation of m/z 325 driven by HO generated m/z 327 and m/z 341. Meanwhile, reactions of m/z 325 with HO and RCS/HOCl/OCl− generated dichlorinated and hydroxylated products (i.e., m/z 377). All the chlorinated products could be further depleted to produce products with less degree of halogenation in the UV/chlorine process, compared to dark chlorination. The acute toxicity to Vibrio fischeri by UV/chlorine was lower than chlorination at the same removal rate of TMP. This study demonstrated the importance of RCS, in particular, ClO, in the degradation of micropollutants in the UV/chlorine process. Display omitted •Trimethoprim degradation by the UV/chlorine process was studied.•Reactive chlorine species (i.e., Cl, Cl2− and ClO) greatly contributed to the degradation.•The contribution of ClO increased with increasing pH and chlorine dosage.•Reactive chlorine species reacted much faster than chlorine to form chlorinated products.•Products with less halogenation degree were formed in UV/chlorine compared to chlorination.