Background and objective NKG2D-expressing NK cells and soluble major histocompatibility complex class Ⅰ-related chain A (sMICA) is one of aroused general interests in tumor research area recently. The aimof the study is to investigate the levels of NKG2D-expressing NK cells and sMICA in peripheral blood of advanced lung cancer which are remarkably related to clinical significance and analyse the role of NKG2D-expressing NK cells and sMICA in immune surveillance. Methods Flow cytometry was used to determine the percentage of NKG2D-expressing NK cells, T cell subsets, NK cells, and ELISA was used to mesure the levels of sMICA in peripheral blood of 115 advanced lung cancer patients and 50 healthy controls. Results Compared with control group, the levels of sMICA、CD8+T cells, NK cells increased, while the levels of NKG2D-expressing NK cells, CD3+ T cells, CD4+ T cells, CD4+ T/CD8+ T in experimental group decreased. NKG2D-expressing NK cells had a perfect negative correlation with sMICA (r =-0.319, P <0.05). NKG2D-expressing NK cells had positive correlation with CD4+ T cells, CD4+ T/CD8+ T and negative correlationwith CD8+ T cells (P <0.05), sMICA had negative correlation with CD4+ T cells, CD4+ T/CD8+ T and positive correlation with CD8+ T cells (P <0.05), they had no significant correlation with CD3+ T cells, NK cells respectively (P <0.05). Conclusion Accumulation of sMICA in serum may lead to the down-modulation of NKG2D-expressing NK which has been proposed to be a novel mechanism used by cancer cells to evade the tumor immunosurveillance. They may be potential indicators investigating immune functions and helpful in the evaluation of their happening and proceeding.