Objective To investigate the effects of c-Jun N-terminal kinase (JNK) 2 on NKG2D-mediated natural killer ( NK) cell cytotoxicity .Me thods NK cells were activated by polyinosinic-polycyti-dylic acid ( Poly I∶C ) .The activation status of JNK signaling pathway was detected .The cytotoxicity of ac-tivated NK cells and the level of IFN-γproduced were measured to determine the function of NK cells in the absence of JNK2.Tumor growth in wild type and JNK2-knockout (JNK2-/-) mice with lymphoma xenograft were measured to evaluate immune surveillance of NK cells .Results The phosphorylation of JNK and up-stream kinases were observed in the early stage of cell activation after treatment of Poly I ∶C.The expressed ligands of the activating receptors NKG2 D significantly increased NK cell cytotoxicity to lymphoma cells . JNK2 deficiency impaired the antitumor effects of NK cells , and then resulted in enhanced tumor growth in JNK2-/-mice.Conclusion JNK2 signaling pathway is involved in the NKG2 D-mediated activation of NK cells and regulates immune surveillance of NK cells against tumor .