The aim of this research was to investigate the removal efficiency of ciprofloxacin (CPX) from aqueous solutions by a novel semi-fluid Fe/charcoal micro-electrolysis reactor and process optimization using response surface methodology (RSM). Effective factors in the removal process including CPX initial concentration, pH, amount of Fe/charcoal, aeration amount and contact time were investigated. The total organic carbon (TOC) removal was determined under optimum conditions of the reactor. The maximum removal efficiency of 95.5% was obtained in optimal conditions as follow; initial concentration of CPX: 17.27 mg/L, pH: 5.38, Fe/charcoal mass: 22.70 g/300 mL, aeration rate: 4.33 L/min and contact time: 105.36 min. The quadratic equation was obtained with a high degree of fit. TOC concentration in optimal conditions decreased from 16 mg/L to 4 mg/L. As a result of this, the Fe/charcoal semi-fluidized micro-electrolysis reactor has a high efficiency in removing drug compounds such as CPX from aqueous solutions. (C) 2019 Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.