Abstract: Diclofenac (DCF) is one of the most frequently detected pharmaceuticals in groundwater, posing a great threat to the environment and human health due to its toxicity. To mitigate the DCF contamination, experiments on DCF degradation by the combined process of zero-valent iron nanoparticles (nZVI) and nano calcium peroxide (nCaO₂) were performed. A batch experiment was conducted to examine the influence of the adding dosages of both nZVI and nCaO₂ nanoparticles and pH value on the DCF removal. In the meantime, the continuous-flow experiment was done to explore the sustainability of the DCF degradation by jointly adding nZVI/nCaO₂ nanoparticles in the reaction system. The results show that the nZVI/nCaO₂ can effectively remove the DCF in the batch test with only 0.05 g/L nZVI and 0.2 g/L nCaO₂ added, resulting in a removal rate of greater than 90% in a 2-hour reaction with an initial pH of 5. The degradation rate of DCF was positively correlated with the dosage of nCaO₂, and negatively correlated with both nZVI dosage and the initial pH value. The order of significance of the three factors is identified as pH value > nZVI dosage > nCaO₂ dosage. In the continuous-flow reaction system, the DCF removal rates remained above 75% within 150 minutes at the pH of 5, with the applied dosages of 0.5 g/L for nZVI and 1.0 g/L for nCaO₂. These results provide a theoretical basis for the nZVI/nCaO₂ application to remove DCF in groundwater.