BACKGROUND & AIMS: Air pollution is a significant public health issue and an important risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), though the underlying mechanisms of this association are unknown. Herein, we aimed to identify metabolic signatures associated with exposure to ambient air pollution and to explore their associations with the risk of MASLD. METHODS: We utilized data from the UK Biobank cohort. Annual mean concentrations of PM RESULTS: A total of 244,842 participants from the UK Biobank were included in this analysis. We identified 87, 65, 76, and 71 metabolites as metabolic signatures of PM CONCLUSION: PM IMPACT AND IMPLICATIONS: Air pollution is a significant public health issue and an important risk factor for metabolic dysfunction-associated steatotic liver disease (MASLD), however, the mechanism by which air pollution affects MASLD remains unclear. Our study used integrated serological metabolic data of 251 metabolites from a large-scale cohort study to demonstrate that metabolic signatures play a crucial role in the elevated risk of MASLD caused by air pollution. These results are relevant to patients and policymakers because they suggest that air pollution-related metabolic signatures are not only potentially associated with MASLD but also involved in mediating the process by which PM