A chimeric antigen receptor targeting to NKG2DL, its encoding sequence, and its modified immune response cells, and the preparation and application of them. This invention constructs a chimeric antigen receptor targeting to NKG2DL and its modified immune response cell based on the NKG2D molecule, and the novel modified immune response cells can effectively target a variety of tumor cells, especially the expression of NKG2DL positive tumor cells, and can be used to prepare preparations for the treatment of tumors. The preparation of the modified immune response cells of the target NKG2DL is easy, and the immune response cells modified by the target NKG2DL have high killing rate to the tumor cells.