Objective To study the change of 11β-HSD2 gene expression in carcinogenesis and cancer prevention and to study the possibility of using 11β-HSD2 gene expression as a molecular target endpoint in the progression of breast cell carcinogenesis suppressed by Grape Seed Extract(GSE). Methods Cell carcinogenesis model for human breast epithelial MCF10A cell was induced by treating the cell with carcinogens NNK and B[a]P repeatedly, and the cell model system for the prevention of carcinogenesis was developed by combining GSE with NNK and B[a]P. Western blot analysis was used to detect the expression of 11β-HSD 2 gene. The biological change of carcinogen treated cells was studied by transfecting small interference RNA (siRNA) to inhibit 11β-HSD 2 gene expression of cells. Results The colony formation of carcinogen treated cells in low-mitogen medium was less after the expression of 11β-HSD 2 gene was inhibited by specific siRNA , which was just like the colony formation of normal cells. The expression of 11β-HSD 2 gene was high in carcinogen treated cells, and the gene expression was low or undetectable in normal breast epithelial cells and cells combined treated with GSE and carcinogen. Conclusion The biological display of carcinogen treated cells could be normalized after the expression of 11β-HSD 2 gene was inhibited. The mechanism for GSE preventing carcinogenesis might be the result of GSE inhibiting the expression of 11β-HSD 2 gene. 11β-HSD 2 gene might be the molecular target endpoint for the suppression of breast cell carcinogenesis by GSE.