Abstract Background: NFATC1 gene is associated with age-related complex traits, including longevity, when it overexpresses. DNA methylation in the NFATC1 gene promoter can downregulate the gene expression. This study aims to examine the association between DNA methylation profile in the NFATC1 promoter and family history of longevity in Chinese population. Methods: We recruited 87 individuals in Bama County, Guangxi in China who were grouped into cases with family history of longevity (n=59, mean age=75.6 years) and controls without family history of longevity (n=28, mean age=57.5 years). The DNA methylation profile in the NFATC1 gene promoter was analyzed by pyro sequencing approach. Results: DNA methylation levels were significantly, positively correlated with age at the sites of 77157888, 77157891, and 77157898 and significantly, negatively correlated with age at the site 77157909. The methylation levels at chromosomal position 77157891 were significantly higher in the case group (β value=0.943) than in the control group (β value=0.911) with p=0.02 for the difference, adjusting for age, gender, smoking, alcohol use and cardiovascular risk factors. DNA methylation levels at site 77157909 were significantly lower in females than in males (p=0.02). Conclusions: The findings of this study suggest that the DNA methylation profile in NFATC1 gene promoter is associated with family history of longevity in the Chinese population.