This paper investigated the effects of selected common chemical species in natural waters (HCO3(-), NO3(-) and humic acids (HA)) on the photodegradation of amoxicillin (AMO) under simulated irradiation using a 300 W xenon lamp. Quenching experiments were carried out to explore the mechanisms of AMO photodegradation. The results indicated that AMO photodegradation followed pseudo-first-order kinetics. Increasing AMO concentration from 100 to 1,000 μg L(-1) led to the decrease in the photodegradation rate constant from 0.2411 to 0.1912 min(-1). The presence of NO3(-) and HA obviously inhibited the photodegradation rate of AMO because they can compete for photons with AMO. Bicarbonate, as a hydroxyl radical (·OH) scavenger, also adversely affected AMO photodegradation. Quenching experiments in pure water suggested that AMO could undergo self-sensitized photooxidation via ·OH and singlet oxygen ((1)O2), accounting for AMO removal of 34.86 and 8.26%, respectively. In HA solutions, the indirect photodegradation of AMO was mostly attributed to the produced ·OH (22.37%), (1)O2 (24.12%) and (3)HA* (20.80%), whereas the contribution of direct photodegradation was to some extent decreased.