In the present work, we shown that: 1) expression of TFPI-2 was repressed in highly invasive breast cancer cell lines; 2) the -84 ~ -36 region was critical for TFPI-2 promoter activity and a KLF6 binding site existed in this region which was abnormally hypermethylated in MDA-MB-435; 3) The CpG methylation in the binding site of KLF-6 blocked the binding of KLF6 to TFPI-2 promoter, diminished the trans-activation of KLF6 on the expression of TFPI-2 gene. The gene discussed is TFPI2; the disease is breast carcinoma.