Hexachlorobutadiene, pentachloroanisole, and chlorobenzenes are regulated to control their release into the environment. There is little information regarding the distribution and risks of these pollutants in Chinese rivers. Therefore, we selected a prosperous agricultural and industrial region in South China as our study area and investigated the contamination profiles and risks of these pollutants in sediment and fish tissue samples. The results showed that, when compared with their levels in sediment, these lipophilic pollutants tended to accumulate in fish tissues in the following order: liver > brain > muscle. Some trichlorobenzene was found to be the result of reductive dechlorination of higher chlorinated benzenes. Hexachlorobutadiene and hexachlorobenzene could pose medium risks at certain sampling sites, but in general, almost no risk was found to the ecosystem. When the estimated daily human intakes of analytes through fish consumption were calculated for different age groups, the results suggested the analytes were unlikely to be a serious health concern for human. Our results could be used to update the existing data on the occurrence of these pollutants in the aquatic environment and to provide information for further pollution control by the local government.