The degradation and mineralization of an antivirus drug acyclovir was attempted by using heterogeneous photocatalytic technology, and the high reactive (OH)-O-center dot was found to be dominantly responsible for the degradation of acyclovir. Thus the frontier electron densities (FEDs) calculation was conducted to predict potential initial sites during the photocatalytic degradation, and the results found that (OH)-O-center dot additions at C8 and C5, and H abstraction at C15, were found to be the three predominant degradation routes for (OH)-O-center dot initiating degradation of acyclovir. Furthermore, the detail degradation mechanisms were also investigated by experimentally identified six major products using HPLC/MS/MS, and the formation possibility of three important products was also calculated to further validate the photocatalytic degradation mechanism with the quantum chemical calculations approach. In addition, to double confirm the proposed degradation mechanisrn, the corresponding kinetic models were proposed to explore acyclovir elimination and the formation of one main product (guanine) over the time profiles. Finally, the potential risk assessment results indicated that the aquatic toxicities at three trophic levels first increased and then decreased rapidly as the total organic carbon decreased. (C) 2014 Elsevier B.V. All rights reserved.