The activation of peroxydisulfate (PDS) by organic compounds has attracted increasing attention. However, some inherent drawbacks including quick activator decomposition and poor anti-interference capacity limited the application of organic compound-activated PDS. It was interestingly found that 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonate) (ABTS) could act as both activator and electron shuttle for PDS activation to enhance diclofenac (DCF) degradation over a pH range of 2.0-11.0. Multiple reactive species of ABTS •+ , • OH, and SO 4 •- were generated in the PDS/ABTS system, while only ABTS •+ and • OH directly contributed to DCF degradation. ABTS •+ , generated via the reactions of ABTS with PDS, SO 4 •- , and • OH, was the dominant reactive species of DCF degradation. No significant decomposition of ABTS was observed in the PDS/ABTS system, and ABTS acted as both activator and electron shuttle. Four possible degradation pathways of DCF were proposed, and the toxicity of DCF decreased after treatment with the PDS/ABTS system. The PDS/ABTS system had good anti-interference capacity to common natural water constituents. Additionally, ABTS was encapsulated into cellulose to obtain ABTS@Ce beads, and the PDS/ABTS@Ce system possessed excellent performance on DCF degradation. This study proposes a new perspective to reconsider the mechanism of activating PDS with organic compounds and highlights the considerable contribution of organic radicals on contaminant removal.