This study aimed to assess the photocatalytic removal efficiency of the fluoroquinolone antibiotic ciprofloxacin (CIP), a pharmaceutically active compound of Ciprocinal®, from the aquatic environment. It focused on evaluating how various influencing factors – radiation type, catalyst loading, initial substrate concentration, CIP source, the introduction of different electron acceptors and scavengers of reactive species, water matrix, as well as photoreactor design – influence the photodegradation efficiency of the antibiotic. Namely, CIP photolytic removal efficiency was enhanced in the presence of H2O2, (NH4)2S2O8, and KBrO3. The highest reaction rate was achieved with a ZnO loading of 1.0 mg/mL, while the degradation rate of CIP increased with the initial concentration across the studied concentration range (0.0025–0.05 mmol/L). Molecular O2 has the best electron acceptor properties in CIP photocatalytic experiments, whereas central role in the degradation mechanism belongs to , h+, and . Next, CIP present in a commercial formulation was more prone to removal than the analytical standard, and its photocatalytic degradation occurs in natural water, however with a reduced removal efficiency compared to ultrapure water. Moreover, reaction intermediates formed during photocatalytic degradation were studied in detail by employing LC–ESI–MS2 technique, whereby the formation of nine degradation intermediates was revealed, and possible CIP degradation patways were proposed. Lastly, ECOSAR model predicted that these intermediates do not pose acute or chronic toxicity towards the aquatic organisms.