Dong (D) lake and the Yangtze (Y) river are the main water supplies of the city of Wuhan, PR China. In the present study, the genotoxic effect of chlorinated drinking water (CDW) processed from raw water of D lake and Y river was evaluated in human HepG2 cells using the Comet assay and the micronucleus test. For that, HepG2 cells were exposed to XAD extracts of CDW corresponding to 0.167, 1.67, 16.7 and 167 ml CDW/ml cell culture. All CDW extracts caused a significant and dose-dependent increase of DNA migration in HepG2 cells. The level of DNA damage varied depending on the sampling time (season) and sampling site. The lowest concentration which caused a significant increase of DNA migration was 1.67 ml CDW/ml culture for water samples collected in August. Water samples collected in March showed their lowest observable effect levels in 167 ml and 16.7 ml CDW/ml culture for Y river and D lake, respectively. Additionally, significant increases of micronuclei (MN) frequencies were found in HepG2 cells after CDW treatment. However, in the MN assay the CDW samples collected in March exhibited higher genotoxicity than the August samples. In conclusion, HepG2 cells provide a useful tool for the detection of genotoxic effects of environmental mixtures.