The entry of gentamicin antibiotics into the aquatic environment has raised many concerns. Today, modern nanotechnology-based approaches have been employed to overcome such problems. The present study was conducted to investigate the efficiency of the UV/ZnO photocatalytic process in removing antibiotic gentamicin from aqueous solution. So we investigated the effects of parameters, including initial gentamicin concentrations (20, 60, and 100 mg/L), zinc oxide concentrations (0, 200, 350, and 500 mg/L), contact times (10, 30, 60, and 120 min), pH (5, 6, and 7), and type of radiation (sun and UV-C). The sample size and the number of test procedures were determined to be 576, taking into account the levels of effective variables and through the full factorial. All experiments were carried out in a double-compartment reactor at laboratory temperature using a magnetic stirrer at 150 rpm. The change of gentamicin concentrations were measured using a DR5000 spectrophotometer. Data analysis and charting were done through Design Expert 8 and Excel 2010 software. Results showed that the maximum removal efficiency of gentamicin of about 93% was obtained under UV-C irradiation at pH of 5, contact time of 30 min, ZnO concentration of 200 mg/L, and initial gentamicin concentration of 20 mg/L. In addition, the maximum removal efficiency of gentamicin (84.32%) under sunlight occurred at pH 6, contact time of 60 min, ZnO concentration of 200 mg/L, and initial gentamicin concentration of 20 mg/L. The results demonstrated that the photocatalytic UV/ZnO process exposed to UV-C or natural sunlight could be an effective process for removing antibiotic gentamicin from the aqueous solution.