Natural killer (NK) cells are effector cells of the innate immune system that exert direct cytotoxic functions. Ubiquitously-expressed toll-like receptors (TLRs) have been recognized as one of the major components promoting dendritic cell (DC) maturation, which may induce polarized immune responses beneficial to cancer immunotherapy. TLR-activated NK cells and DCs are prerequisite for robust activation of the innate immune system against tumors. Recently, some medical research and clinical trials have proposed NK cells as a new therapy and potential strategy in both children and adults with those cancers which cannot be cured with the usual treatment modalities. As an example, the importance of DC/NK antitumor immunity in the outcome of breast and other cancers is recently recognized. Therefore, considering strategies which exploit TLR-mediated immunity in concordance with DC/NK system holds strong potential for cancer therapy. This review addresses the current knowledge about the potential role of TLR in tumor immunotherapy