Photocatalytic activity of NiO incorporated into clinoptilolite nanoparticles (NiO-NCP) was studied in the photodegradation of cotrimaxazole pharmaceutical capsule (a mixture of trimethoprim and sulfamethoxazole) in aqueous system under medium Hg-lamp irradiation. Samples were characterized by XRD, FT-IR, UV-Vis-DRS, TEM and BET. The effects of some key experimental parameters affecting the photodegradation extent of the pollutant were studied and the best results were obtained at 13.2% NiO loaded onto NCP, 0.2 g L-1 of the NiO13.2%-NCP catalyst, 50 folds diluted cotrimaxazole solution at pH 3. COD of the pollutant solution was decreased from its initial value of 1930-700 mg L-1 during 4 h photodegradation process (corresponds to 64% degradation of cotrimaxazole). The peak area of the main peak in HPLC chromatogram was also decreased during the irradiation process. HPLC and COD results are in accordance with decrease in UV-vis absorbance during the photodegradation process, confirming the degradation of cotrimaxazole into smaller fragments. (C) 2016 The Institution of Chemical Engineers. Published by Elsevier B.V. All rights reserved.