Fenitrothion (FNT), a common organophosphorus pesticide, has been regarded as a contaminant because it is adverse to the environment. In this study, we chose the highly effective technique, persulfate (PS) activation by zero-valent iron powder (Fe-0), to degrade FNT. The effects of several experimental parameters including PS and Fe-0 dosages, pH, temperature, and common natural water constituents were systematically investigated via kinetics studies. We found that the addition of Fe-0 significantly enhanced the FNT degradation by PS under any of the studied conditions. Under the optimal conditions of [FNT]:[PS] = 1:500 (molar ratio), Fe-0:PS = 1:1.5 (molar ratio), pH = 3.0, and 35 degrees C, 10 mg L-1 of FNT could be completely degraded in 45 min and 20 mu g L-1 FNT was removed 96 +/- 0% in 12 h. Sulfate (SO4-) radicals led the degradation of FNT in the Fe-0/PS system. Twelve transformation products of FNT were determined by LC-MS/MS analysis, and the vulnerable sites in FNT were predicted by a density-functional-theory-based descriptor, 2 Sigma(C-ri(HOMO))(2), to illustrate the generation of initial reaction products. The overall acute and chronic toxicity of FNT and its products, as predicted by the ecological structure-activity relationship model (ECOSAR), decreased in the Fe-0/PS process. The present work proves that FNT could be efficiently degraded by Fe-0-activated PS, which may also contribute to future research on the removal of other organophosphorus pesticides.