In this study, the transformation and detoxification of sulfamethoxazole (SMX, a frequently detected antibiotic in the environments) by permanganate (Mn(VII)) in the presence of model humic constituents (HCs) was evaluated. SMX that hardly react to Mn(VII) was rapidly degraded by Mn(VII) in the presence of catechol (CAT) at pH 5-7, while resorcinol (RES) and hydroquinone (HQ) showed negligible accelerating effect. This enhancing effect was attributed to the 1,4-nucleophilic addition between SMX and o-benzoquinone (o-BQ), an important intermediate generated from oxidation of CAT by Mn(VII). Both Mn(VII) and in-situ formed manganese dioxide (Mn(IV)) accounted for the generation of o-BQ. The experimental results indicated that alkaline condition and excess Mn(VII) were unfavorable for the degradation of SMX by inhibiting the formation of o-BQ. Bioluminescence inhibition assay with vibrio fischeri and data simulated by EPI software showed that the transformation products of SMX retained much less acute toxicity than the parent SMX. Furthermore, the effect of several other HCs structurally related to CAT on the abatement of SMX was explored. The result suggested that the accelerating effect of CAT analogues largely depended on the type of substituent group in para position. Meanwhile, the concentration of manganese in the supernatant was lower than WHO criteria (0.1mg/L). This work provided a novel and efficiency strategy to detoxify SMX in water treatment.