Objective The phenotypes of population, such as biogeographical and physical characteristics, are the result of the interaction between genotype and environment. A large number of genomic studies have shown that the Han Chinese are admixed population which displayed obvious genetic differences between the north and the south. The purpose of this study is to explore whether there are differences in epigenomes between northern and southern Han populations, and to screen biogeographical specific genetic loci.Methods Glint software was used to perform epigenome-wide association study (EWAS) analysis on genome-wide methylation microarray data of 483 Han Chinese individuals, and Lasso regression was used to screen the sites. Multiple logistic regression algorithm was used to construct the prediction model for the Han population in the south and the north, and the evaluation was conducted by the method of 10-fold cross validation.Results A group of CpG sites with significant differences between southern and northern Han populations were screened out, with accuracy of 99.03% and Kappa of 0.979 6.Conclusion This study shows that there are epigenetic differences between the southern and northern Han populations, which lays a foundation for further studies on epigenetic differences between the Han populations in different regions.