Display omitted •kapp of isoproturon and chlorotoluron reacting with SO4•− and HO• were determined.•QSAR model implied the great effect of ring substituents in phenylureas on UV/PS behaviors.•Effects of PS dosages, UV intensity, pH and water matrixes (ions and NOM) were examined.•The UV/PS destruction pathways of phenylureas were proposed by MS analysis.•Compared with UV and UV/H2O2, UV/PS was superior in controlling the DBPs formation. The degradation performance of selected phenylurea herbicides (isoproturon and chlorotoluron) by UV/persulfate (PS) as well as toxicity assessments associated with disinfection by-products (DBPs) in subsequent oxidation were comparatively studied. The elimination of herbicides followed pseudo first-order kinetics well. Then effects of UV intensity, pH, PS dosage and water matrix (background ions and Nature organic matter (NOM)) were investigated detailedly. Increased kobs values were observed at higher PS dosages and greater UV intensity, but the degradation was basically resistant to pH variation. kobs could be inhibited by coexistent ions and NOM. Radical scavenging study revealed the more important role of sulfate radical (SR, SO4•−) than hydroxyl radical (HR, HO•). kapp of HO• and SO4•− towards isoproturon and chlortoluron were determined respectively. The results also indicated that the relative reactivity of alkyl- or halogen- substituted phenylurea herbicides with HO• and SO4•− can be correlated with Hammett constants as the molecular descriptor. Then a quantitative structure-activity relationship was established to predict the structure-dependent reactivity of phenylurea herbicides by UV/PS concerning substituent effects. The energy demand of UV/PS system was evaluated. The degradation intermediates by direct UV, UV/H2O2 as well as UV/PS were comparatively identified and the related destruction pathways were postulated. Compared with UV and UV/H2O2, UV/PS was superior in controlling the DBPs generation in post-disinfection of these herbicides. The data supported that SR-advanced oxidation processes (AOPs) had more advantages in removal efficiency and toxicity control than HR-AOPs. This study provided some theoretical bases for the UV/PS degradation behaviors of structurally similar phenylurea herbicides with regard to different substituents on the aromatic ring.