This study systematically investigates the photocatalytic degradation of cephalexin (CEP), an anthropogenic antibiotic, in aqueous solution using anatase titania nanoparticles (TiO2 NPs) activated under 365-nm light. By inspecting the effects of operational parameters, such as irradiation time, CEP concentration, pH of medium, photocatalyst dosage, and temperature, the photocatalytic degradation kinetics, mechanism, and thermodynamics of the antibiotic were described based on the empirical Langmuir–Hinshelwood, Weber-Morris, Arrhenius, and Eyring models. The results revealed two distinct rate constants for CEP photocatalytic degradation; 0.023 min‒1 and 0.422 min‒1, with an activation energy of 3.949 kJ mol‒1. At concentrations up to 20 mg L‒1, CEP is completely degraded by 0.5 g L‒1 TiO2 NPs. The photocatalytic degradation process was accelerated in the presence of H2O2. Thermodynamic analysis indicated that CEP degradation is non-spontaneous and endothermic, and reduces disorder on the photocatalyst surfaces. Liquid chromatography-mass spectrometry was used to identify the photocatalytic degradants. The proposed degradation pathways of CEP involved the ring opening of the β-lactam moiety, driven by redox reactions of the antibiotic with free radicals generated on the photocatalyst surfaces, followed by hydroxylation, decarboxylation, and demethylation. Antibacterial activity studies suggested that the photocatalytic degradants are less detrimental to the aquatic environment than the parent antibiotic. © Akadémiai Kiadó Zrt 2025.