Wastewater discharges containing high nitrogen levels can be toxic to aquatic life and cause eutrophication. In this study, the application of the SHARON (Single reactor for High activity Ammonium Removal Over Nitrite) process for the treatment of refinery wastewater (sour water) was evaluated, in view of its coupling with the ANAMMOX (ANaerobic AMMonium OXidation) process. A Continuous Flow Stirred Tank Reactor was initially fed with a synthetic medium, and the applied NH₄-N concentration and wastewater/synthetic medium ratio were progressively increased up to 2000 mg_N/L and 100%, respectively. Despite the high potential toxic effect of the real wastewater, overall SHARON performance did not decrease with the increasing real wastewater/synthetic medium ratio, and biomass showed progressive acclimation to the toxic compounds in the real wastewater, as demonstrated by toxicity assessments. NH₄-N and dissolved organic carbon removal efficiency were around 50% and 65%, respectively. Moreover, the effluent was characterized by a NO₂− N/NH₄-N ratio of 0.9±0.01 and low nitrate concentration (<30 mg_N/L), in line with the requirements for the subsequent treatment by the ANAMMOX process.