In the present work, the synthesis, characterization, and photocatalytic performance of CuS nanopowder were studied. The achieved photocatalyst was characterized by X-ray diffraction, Scanning Electron Microscopy, X-ray photoelectron spectroscopy, and Brunauer-Emmett-Teller. The degrading characteristic of CuS photocatalyst was investigated during 100 min and 18 h under visible radiation (Vis irradiation) for degradation of Ofloxacin (OFX), revealing a good degradation rate of OFX. Over 100 min of degradation, some by-products that can be considered as secondary pollutants were produced. Then, to destroy these pollutants the radiation time was increased up to 18 h. The results showed a perfect degradation of OFX and its secondary pollutants. The effective variables including pH, degradation time, and photocatalyst dosage were optimized and studied in multivariate method by design expert7 software. Moreover, the kinetic of the process was evaluated, showing accordance with Langmuir-Hinshelwood model. Recognition of the products was carried out by ultra performance liquid chromatography-tandem mass spectrometer. The synergic effect of CuS adsorbent-photocatalyst exhibited a good adsorption-degradation rate of OFX under Vis irradiation.