Abstract: Isotope fractionation effect of organic pollutant transformation facilitates a deep understanding of reaction mechanism, and potentially contributes to risk assessment and remediation of contaminated environments. Hexachlorocyclohexanes (HCHs) had been used as pesticides for a long time. They have been classified as persistent organic pollutants (POPs) due to their stability in chemical properties and long half-life in the environment. In recent decades, significant advances were achieved in the isotope fractionation research of HCH transformation and in the isotopic analysis of environmental HCHs, reflecting the state-of-the-art theories and applications in this field. In this review, following a brief introduction to the phenomenon of isotopic fractionation and the compound specific isotope analysis (CSIA) technique, the isotopic effects of HCH transformation were discussed, with an emphasis on the applications of novel technologies, such as dual-element isotope analysis and enatioselectivity analysis. Subsequently, the uses of isotope fractionation in pollutant traceability, food chain transmission, transformation in soil-plant systems and natural attenuation assessment were presented. These progresses demonstrate the potential applications of isotope fractionation in risk assessment and clean-up of environmental organic pollutants.