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In this study, the effect of seasonal variation and Fe(III) concentrations on the formation and distribution of trihalomethanes (THMs) and haloacetic acids (HAAs) during chlorination of treated water samples from Yangzte River were examined The corresponding lifetime cancer risk of THMs and HAAs was also estimated using the parameters and procedure issued by US Environmental Protection Agency. The results indicated that the mean concentration of THMs (mean, 108.1 μg/L) are significantly higher than that of other seasons, which is related to high bromide ion in raw water during the salt intrusion, and while five HAA5 concentrations were higher in autumn (mean, 25.0 μg/L) than those of other seasons. At the same time, in presence of Fe(III) increase THMs and HAA5 levels. Total cancer risk in spring (1.16×10-4) increased about 2 times than those of summer (5.36×10-5) in our experimental conditions. In addition, in the presence 0.5 mg/L Fe(III), cancer risk increased 10% in spring than those in the absence of Fe(III) under the same conditions. Results showed that the lifetime cancer risk for THMs and HAAs followed the order, oral, inhalation, and dermal Thus, the seasonal and Fe(III) effects need to be considered in human health risk assessment studies, especially in the area of coastland and estuary area.