Abstract NKG2D is an improtant activating receptor of the innate immune system, which starts innate immune surveillance and immune clearance in the early stage of tumorigenesis. NKG2D and its ligands can also be regarded as a kind of tumor marker, serving as a crucial prognostic factor and indicator in the formulation of treatment protocols. Meanwhile, tumor cells can downregulate the expression of NKG2G/NKG2DL by means of varied humoral or cellular immunity pathways, mediating its immune escape effect. We hope that after intensive studies on NKG2D/NKG2DL pathways, we could find some new approaches against cancer, underlying substantial foundations in future individualized immunotherapy. In this review, we present the role of NGK2D receptor and its ligand in tumor immunity.