Breast cancer is the most frequently diagnosed cancer in women. In these studies, a metastasis suppressor gene, KISS1 and its truncated fragment, were overexpressed in the breast cancer cell line MDA-MB-231. In addition, KISS1 expression was downregulated in MDA-MB-157 cell line using a KISS1-specific siRNA. The effects of KISS1 on breast cancer cells both in vivo and in vitro were then identified. Our results indicate that KISS1 can induce apoptosis and inhibit mobility of breast cancer cells. Moreover, the expression of KISS1 in established xenografted tumors was associated with a decrease in tumor size and weight. Accordingly, the survival rate of these mice was significantly higher compared to that of mice bearing tumors that did not express KISS1. We also confirm that KISS1 could decrease the number of circulating tumor cells (CTCs). The plasma levels of metastin and the number of CTCs were significantly positively correlated. Furthermore, we found that KISS1 can inactivate p-MEK and p-ERK. Overall, these studies demonstrate the antitumor activity of KISS1 in the breast cancer cell lines and provide insight into relevant mechanisms that may lead to novel treatments for breast cancer.