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Objective: The expression and the methylation level of the CpG island in its promoter of Foxa2 were explored during cellular replicative senescence and premature senescence induced by hydrogen peroxide of human embryonic lung fibroblasts (HEFs).Methods: The mRNA level of Foxa2 was detected by Q-PCR in different groups during cellular senescence of HEFs.The methylation status in the promoter region (-777 bp~-478 bp) was observed by methylation-specific PCR.The CpGs island methylation level was detected by bisulfite sequencing.Results: The mRNA level of Foxa2 went down during cellular senescence of HEFs.The mRNA level was decreased by 51% and 80% respectively in replicative senescence and premature senescence and no distinct change in mid-aged cells.It had a certain methylation level in-777 bp~-478 bp of premature senescence group.The average rate of methylation was 5.7% in the young cells, 17.1% in the replicative senescent cells and 43.6% in the premature sensescent cells.Conclusion: The increasing methylation of CpG island in the promoter of Foxa2 is involved in regulating its mRNA expression during cellular senescence of HEFs.