Nonsteroidal anti-inflammatory drugs (NSAIDs) are a family of pharmaceuticals with an extensive prescription where it is often detected in environmental samples. This work studies the oxidation of Piroxicam (PIR) as a representative NSAIDs using the UVC-activated persulfate process. While direct UVC photolysis removed only 10% of 1 mg / L of PIR after 20 min, the addition of 12.5 mg / L persulfate eliminated the drug in less than 4 min. PIR removal follows pseudo-first-order kinetics and the apparent kinetic constant decreased from 0.74 to 0.158 min−1 when the initial concentration increased from 0.5 to 3 mg / L. The presence of inorganic ions such as bicarbonates and chlorides reduced PIR removal slightly, and the kinetic constant decreased from 0.559 for ultrapure water to 0261 and 0.522 min−1 for 250 mg/L bicarbonates and chlorides, respectively. At the opposite, the presence of humic acid significantly increased the treatment time required since PIR removal after 7.5 min was 100%, 76%, and 43% for ultrapure water, 10 and 20 mg/L humic acid respectively. The effect of the pH was minimal, thus allowing the application of the process in a wide range of pH. In the experiments that were performed in the actual matrix while the efficiency was delayed in the case of the organic effluent. The change in toxicity expressed as inhibition of bacterium Vibrio Fischer does not follow the reduction of PIR in secondary effluent implying the generation of possibly toxic intermediates by oxidation of both PIR and the aqueous matrix.