Objective:To explore the relationship between genetic and epigentic modification of CTSD gene enhancer and breast cancer metastasis. Methods:CTSD gene enhancer sequence was detected in 152 cases of breast cancer specimens and paracancerous tissues using PCR amplification. CTSD gene enhancer demethylation state was observed in breast cancer by methylation-specific restriction enzyme digestion combined with PCR amplification. Results:There is no meaningful mutational site in CTSD gene enhancer sequencing. Our genetic research shows that incidence of methylation are 85.3% in metastatic breast cancer enhancer and 51.9% in non metastatic breast cancer. However no methylation is observed in paracancerous tissues. So both of the methylation incidence in metastatic and non-metastatic tissues are significantly different from that in paracancerous tissues. Conclusion:The functional regulation in CTSD gene enhancer does not suffer from the influence of genetic mutations. The demethylation incidence in CTSD enhancer is high related to metastasis of breast cancer. Therefore,demethylation level in CTSD gene enhancer may be the prognostic indicator of breast cancer.