The optimum operating conditions for TiO2 photocatalytic degradation of tetracycline antibiotic (TC) in aqueous solution and the role of active oxidative species (AOS) from UV/TiO2 in its degradation were investigated. Response surface methodology (RSM) and central composite design (CCD) were adopted to optimize three parameters: TiO2 concentration, initial pH and UV irradiation time. Radical scavengers were added to reaction solution to assess the photocatalytic reaction mechanism of TC. The results showed that 93.1% degradation efficiency was obtained under optimum conditions established during experimentation (TiO2 concentration = 2.09 g l(-1), pH = 5.56 and t = 20.95 min). These results agree with the prediction made by the proposed model. Photocatalytic degradation of TC followed a pseudo first-order reaction rate. Photogenerated holes (h+(VB)) with minor participation from superoxide anions (O2*), were responsible for TC oxidation on TiO2, while hydroxyl radicals (*OH) played a negligible role in titania-TC oxidation.