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Halogenated methyl sulfonic acid (HMSAs) is a new type of disinfection by-product recently reported, and there are few relevant studies, so its source and harm are still unclear. This study mainly discusses the source of halogenated methyl sulfonic acid from the macroscopic level and evaluates the harm to human health. This study clarified that chlorine disinfection is one of the main ways of generating halogenated methyl sulfonic acids (HMSAs) in drinking water. The macroscopic properties of HMSA precursors were analyzed through liquid chromatograph-mass spectrometry (LC-MS/MS), 3D fluorescence, and Fourier transform infrared spectrometry. The results showed that polar and positively charged organic compounds with molecular weights of >3 KDa or <0.5 KDa can readily generate HMSAs. By analyzing the main components of natural organic compounds in water and comparing them with the characteristics of organic compounds such as dimethyl sulfoxide and ethyl mercaptan, it meant that natural organic compounds are easily degraded. Humic and fulvic acids contribute the most to HMSA generation. This study lasted for three years and collected water samples from 102 waterworks in 24 cities in China, and the existence of HMSAs in drinking water in different cities was analyzed. The potential health risks associated with HMSAs were used by the United States Environmental Protection Agency (U.S. EPA) health risk assessment model. The average and maximum concentrations of HMSAs in tap water from key cities in China were taken as evaluation objects. The results showed that the carcinogenic risk coefficient (R) value of both concentrations was far lower than the lowest acceptable carcinogenic risk (1.0 × 10−6) provided by U.S. EPA. Therefore, HMSAs in drinking water in China currently pose no human health risks. • Chlorine disinfection is one of the reasons for the production of halogenated methyl sulfonic acid (HMSAs) in drinking water. • The natural organic matter easy to degrade in water is macro precursor of HMSAs. • Humic acid and fulvic acid are the main factors of HMSAs produced by chlorine disinfection. • HMSAs in drinking water in China has little impact on human health. [ABSTRACT FROM AUTHOR]