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In this work, heterogeneous catalytic ozonation for the treatment of bio-treated saccharin sodium production wastewater (BSSW) was comprehensively investigated with pilot- and full-scale systems, with special emphasis on the effects of Cu 2+ in the original wastewater on catalyst activity. The results of semi-batch and continuous experiments show that heterogeneous catalytic ozonation was effective in removing organic compounds from high-salinity wastewater and that Cu 2+ in the original wastewater had a substantial effect on the performance of the process. The retention of 0.15 mM Cu 2+ in BSSW increased the chemical oxygen demand (COD) removal by 31% in semi-batch reactor with heterogeneous catalytic ozonation. The stable COD removal efficiencies ranged from 74% to 66.4% for a 9-month operation, indicating that Cu 2+ with an appropriate concentration in the original BSSW not only improved the COD removal efficiencies but also inhibited catalyst deactivation; catalyst deactivation was mainly caused by the deposition of inorganic salts on the catalyst surface. Cu 2+ combined with some anions to inhibit the formation and deposition of inorganic salts that could easily cause deactivation. The deposited copper salts were readily eliminated, especially during backflushing operations. Moreover, in a full-scale study, heterogeneous catalytic ozonation with 0.15 mM Cu 2+ in BSSW exhibited stable COD removal efficiencies (51%-83%) after over 3 years of operation. This study offers a new idea for using the inherent properties of wastewater to perform advanced treatments on high-salinity industrial wastewater through heterogeneous catalytic ozonation., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2022 Elsevier Ltd. All rights reserved.)