Iohexol can hardly be removed in conventional wastewater treatment processes due to its non-biodegradable and hydrophilic characteristics. In this study, a kinetic model was established to describe iohexol degradation in Fe (II)-activated persulfate system. The developed model can well predict iohexol degradation and evolution of sulfate radical with various initial iohexol and oxidant (ferrous iron and persulfate) concentrations under various water matrix. The rate constant of iohexol reacting with sulfate radical was calculated as (1.83 +/- 0.10) x 10(9) M-1 s(-1). The effects of the two most common components in natural water bodies, chloride ion and natural organic matter (NOM) on iohexol degradation, were also studied. Both experimental data and model results showed that the low concentration of chloride ion promoted iohexol degradation while high concentration inhibited it, and NOM slightly inhibited iohexol degradation. Besides, radical quenching tests were employed to identify the main radicals formed in the system and further verified the model accuracy. The model is also capable of predicting the atrazine degradation with the correlation coefficients between the experimental data and predicted results above 0.97, suggesting the applicability of the established model for some other recalcitrant contaminant degradation in the Fe2+/PS system.