Natural killer (NK) cells are the prototype innate lymphoid cells endowed with potent cytolytic function that provide the first line of host defence against microbial infection and tumors. NK cells are now considered to be an important part of the immune system by controlling microbial infections and tumor progression. Although they were discovered more than 40 years ago, NK cells have recently been attracting attention for their potential in immune-based therapies. Over the past few years many researchers have reported that NK cells as one of the main effector cells of the innate immune system, their activity and function are greatly influenced by the cell surface protein glycosylation modification and glycan-binding proteins (e.g. siglec, selectin and galectin) located on the surface of cells. For example, the immune evasion mechanisms from NK immunity using cell-surface glycans have been identified. The cancer cells use the certain types of cell-surface glycans to evade NK immunity, such as reducing NK activating receptor-mediated signaling, enhancing NK inhibitory receptor-mediated signaling, and modulating TRAIL-mediated killing. In addition, such siglec interacts with sialic acid-overexpressing cells to lead to inhibition of NK cells activation. Selectin combines with ligand to promote the immune function of NK cells. Galectin binds β-galactosides to mediate NK cells immune process. This review summarizes the recent progress of the certain types of glycans and glycan-binding proteins related to the immunological function of NK cells, and discusses the influence of abnormal glycan-binding proteins for the development of tumor, as well as their application prospect in immune-based therapies.