Extensive epidemiological studies have established the association between exposure to early-life adversity and health status and diseases in adults. Epigenetic regulation is considered as a key mediator for this phenomenon but analysis on humans is sparse. The Great Chinese Famine lasting from 1958 to 1961 is a natural string of disasters offering a precious opportunity for elucidating the underlying epigenetic mechanism of the long-term effect of early adversity. Using a high-throughput array platform for DNA methylome profiling, we conducted an epigenome-wide association study on early-life exposure to Chinese famine in adults born during 1959-1961 and compared to unexposed subjects born 1963-1964. The single CpG site analysis of whole epigenome revealed a predominant pattern of decreased DNA methylation levels associated with fetal exposure to famine. Four CpG sites were detected with p <1e-06 (linked to EHMT1, CNR1, UBXN7 and ESM1 genes), 16 CpGs detected with 1e-06< p <1e-05 and 158 CpGs with 1e-05< p <1e-04, with a predominant pattern of hypomethylation. Functional annotation to genes and their enriched biological pathways mainly involved neurodevelopment, neuropsychological disorders and metabolism. Multiple sites analysis detected two top-rank differentially methylated regions harbouring RNF39 on chromosome 6 and PTPRN2 on chromosome 7, both showing epigenetic association with stress-related conditions. In conclusion, results from this study provide new clues to the epigenetic embedding of early-life adversity and its impacts on adult health. Funding Statement: This study was financially supported by Independent Research Fund Denmark grant number DFF – 6110-00114. Declaration of Interests: None declared. Ethics Approval Statement: This study was approved by the Ethics Committee of Qingdao CDC. Written informed consents were obtained from all participants.