The degradation of pyrazinamide (PZA) by electron beam irradiation (EBI) was studied. It was found that the degradation of PZA was efficient with the removal rate of 99% for 0.2 mM PZA under 5 kGy, and the degradation kinetics followed pseudo-first-order kinetics. The presence of CO32−, HCO3−, NO3−, and fulvic acid inhibited the degradation of PZA. The addition of H2O2 or K2S2O8 effectively enhanced the degradation and mineralization of PZA. The scavenger experiments and quantum chemical calculations showed that ·OH was the primary reactive species in the degradation. The identification of intermediates and quantum chemical calculations illustrated the mechanism of degradation. [ABSTRACT FROM AUTHOR]