Abstract: Natural killer receptors (NKRs) and Toll-like receptors (TLRs) are the most important receptor supfamilies in innate immunity and act as first line of host defense against infection or transformed cells. These receptors exert peculiar recognition mechanisms to sense danger signals and distinguish infectious nonself from noninfectious self, and thereafter work as link molecules between innate and adaptive immunity. NK cells are the most important lymphocytes population, recognize infection and tumor at initial, and play a critical role in linking innate immunity with adaptive immunity. In this paper, we highlight the importance of recognition and interaction of those receptors via NK cells. The precise mechanisms can be harnessed to aid the rational design of therapy against infection, inflammation, cancer or autoimmune diseases.