Systemic administration of Salmonella to tumor-bearing mice leads to the preferential accumulation within tumor sites and retardation of tumor growth. The cancer stem-like cell (CSC) hypothesis suggests that CSCs are the root of cancer and induce metastasis and recurrence. The objective of this study was to examine if Salmonella could inhibit the growth of CSCs derived from mouse breast cancer. Systemically injected Salmonella preferentially accumulated within tumors for at least three weeks and the bacteria accumulated preferentially not only in subcutaneous but also in orthotopic tumors over livers and spleens at ratios ranging from 1000:1 to 10,000:1. Salmonella were capable of delaying tumor growth and enhancing survival in both subcutaneous and orthotopic tumor models. More strikingly, Salmonella acted to retard tumor growth and extensively prolong the survival time of the mice bearing CSC-induced tumors. Our results also found that Salmonella predominantly, although not exclusively, resided in the CSC regions of the tumor. These data suggest that Salmonella can inhibit the growth of breast cancer by targeting the CSC niche. In conclusion, Salmonella can be used for the management of breast cancer.