B7-H6 is a co-stimulatory molecule discoveried recently. B7-H6 is not expressed on normal cells, but specially expressed on tumor cells. It can also be expressed on antigen presenting cells (APC) by the induction. The B7-H6 expression can be downregulated by HDACi. NK cells can be activated to release TNFα and IFNγ through B7H6-NKp30 pathway. The B7-H6 molecules expressed on the cell surface can be shedded to form soluble molecules. In the meantime, the B7-H6/NKp30 pathway may be involved in the pathogenesis of primary Sjogren syndrome. B7-H6/NKp30 may become a new therapeutic target for tumor, inflammation and autoimmune diseases. This review discusses the B7-H6 and receptor sructure, the expression and significance of B7-H6, the function and regulating mechanism of B7-H6 and the soluble molecules of B7-H6.