In this study, the degradation of propranolol (PRO) by UV/persulfate process was systematically investigated. Direct photolysis of PRO was limited due to its low quantum yield, while the PRO degradation efficiency can be greatly promoted by the combination of persulfate and UV irradiation. Radical scavenging tests showed that both SO4– and OH contributed to the removal of PRO, with SO4– playing a more important role. The degradation rate of PRO was improved by increasing the persulfate dose and initial solution pH consistent with pseudo-first-order reaction kinetics. The effects of common water constituents were species dependent. HCO3− and Cl− promoted PRO degradation. By contrast, NO3− and HA were found to inhibit PRO degradation. A total of nine degradation products were identified by LC/MS/MS, which mainly derived from the ring-opening attack on the naphthalene group or oxidation of the amino moiety by SO4– and OH. Finally, the toxicity of the reaction mixtures was also assessed using luminescent bacteria Vibrio fischeri, and the results indicated that UV/persulfate is capable of controlling the toxicity of PRO degradation. Display omitted •UV-activated persulfate was applied on PRO oxidation.•Various factors influence PRO degradation to different extent.•Naphthalene ring and amino moiety in PRO molecule were two reactive sites.•UV/persulfate is capable of controlling the toxicity during PRO degradation.