Introduction: Breast cancer is the most common cancer in women, and tumor resistance to chemotherapy is one of the major causes of failure in its treatment. A dynamic association between breast cancer and the immune system is essential for this cancer incidence, growth, and metastasis. Emerging evidence suggests that chemoresistance in breast cancer can promote with Toll-like receptors 4 (TLR4), as an important pattern recognition receptor in innate immunity. In this review, we describe the link between TLR4 function and breast cancer chemotherapy.Description: TLR4 expresses not only on immune cells, but also on tumor cells. It can be activated by endogenous ligands produced by host-damaged cells and chemotherapeutic drugs such as paclitaxel. The activation of TLR4 up regulates the expression of various inflammatory cytokines and metalloproteinases that enhance tumor motility and local inflammation. This proinflammatory shift protects cancer cells from death induced by chemotherapy and equips them with the ability to leave the primary site. Also, the release of excessive levels of inflammatory cytokines in the blood can cause bone marrow progenitor cell mobilization to the tumor. TLR4 induced inflammatory after chemotherapy can also promote epithelial-mesenchymal transition. Increased metastatic potential of tumor cells, with high blood and lymph vessel density, results in local recurrence and distant metastasis. On the other hand, stimulation of TLR4 pathway in immune cells might have both pro- and anticancer consequences. For example, the role of TLR4 in antigen-presentation of immune cells and recruitment of cytotoxic T-cells. This may result in decreased primary tumor growth due to chemotherapy-induced TLR4 signaling in BM- derived cells and other immune cells.Discussion and conclusion: TLR4 stimulation in breast cancer chemotherapy has a double-edged sword effect as an anti- or pro-tumoral effect. So further research on the role and mechanisms of TLR4 activation in chemotherapy is needed to improve breast cancer survival rates.