Chironomid larvae propagated excessively in eutrophic water body and could not be effectively inactivated by the conventional disinfection process like chlorination due to its stronger resistance to oxidation. In this paper, a pilot-scale study of chlorine dioxide preoxidation cooperating with routine clarification process for Chironomid larvae removal was conducted in Shenzhen Waterworks in Guangdong Province, China. The experimental results were compared with that of the existing prechlorination process in several aspects, including the Chironomid larvae removal efficiencies of water samples taken from the outlets of sedimentation tank, sand filter, the security of drinking water and so on. The results showed that chlorine dioxide might be more effective to inactivate Chironomid larvae than chlorine and Chironomid larvae could be thoroughly removed from water by pre-dosing chlorine dioxide process. The GC-MS examination and Ames test further showed that the sort and amount of organic substance in the treated water by chlorine dioxide preoxidation were evidently less than that ofprechlorination and the mutagenicity of drinking water treated by pre-dosing chlorine dioxide was substantially reduced compared with prechlorination.