Natural killer cell, also known as large granular lymphocytes, is an independent and non-specific immune cell. It has no MHC restriction to target cells recognition and destruction, and it can directly kill tumor cells and virus-infected target cells without antigen pre-sensitized. It also can produce a large number of immune-active cytokines to enhance or expand its antitumor effect, which can be regarded as the first line of the host defense system. Several experimental evidences demonstrated the important role of NK cells in the elimination of tumor cells. Vivier et al report that a low NK cell cytotoxicity in peripheral blood was correlated with an increased cancer risk. Furthermore, NK cells infiltrating in the tumor tissue was associated with good prognosis in colorectal, gastric, and lung BKM120 cancers. With the development of tumor formation, malignant tumor cells and infiltrating immune cells interact and composed the tumor micro-environment. Most of studies published showed that a large number of immune cells infiltrating into tumor tissue played an important role in improving tumor prognosis. But as we all known, the prognosis of lung-associated malignancies is very terrible, even though there are many immune cells in the lung. We want to know if there is a differential composition of the immune cell infiltrate in malignant and non-malignant lung tissue areas, and even might potentially contribute to this effect. Esendagli G et.al found that in non-small cell lung cancer patients, NK cells were not almost found in the malignant tissue regions, non-malignant counterparts were selectively populated by NK cells and those NK cells showed strong cytotoxic activity ex vivo. So the impact of NK cell receptor expression and function may be different caused by the interaction between NK cells and tumor in the tumor micro-environment. By exploring NK cells in the body and/or lung cancer micro-environment, discuss its distribution, receptor expression, functional status with lung cancer invasion, metastasis and prognosis, clarify the mechanism of NK cells involved in lung cancer micro-environment from the cellular and molecular levels. This study revealed that NK cells infiltration and NK cells receptor expression change in NSCLC tumor environment. From our research, we found that the NK cells infiltrated mainly in the tumor stroma, constituting the tumor micro-environment. These observations are in agreement with previous observations demonstrating that lung tumor micro-environment. In addition, we got the surprise that the number of NK cell infiltrating in lung cancer tissue is closely related to the pathological types, size of the primary cancer, smoking history and prognosis of the patients with lung cancer. Previous literature implied that some molecules expressing in the tumor and some mediums released from tumor commonly led to tumor escape mechanisms from NK cell immunological surveillance. And to the same patients there were significant differences between the peripheral blood NK cell phenotype with in tumor. The NK cell surface receptor DNAM-1, 2B4, CD16 expression reduced in ovarian cancer, which can result in the NK cell activation function were badly damaged. Our research result prompt that the activated receptor of NK cells is down-regulated and inhibitory receptor of NK cells is upregulated in the transplanted tumor and the distant metastatic lesions of human large cell lung cancer cell lines, which might be the main reason leading to NK cell killing ability decreased. NKG2D is a receptor for MHC class I chain-related A and B molecules, which are frequently expressed by epithelial cancers. Ligation of NKG2D induces anti-tumoral effector functions in both NK and T cells.