Lung cancer is one of the most malignant common tumor worldwidely and it's the most popular cancer in China. Both the prevalence and mortality of it are higher than other cancers. And its 5-year survival rate is 15%. Non-small cell lung cancer(NSCLC) accounts for about 85% lung cancer and its pathogenesis has not been elucidated. Therefore, early prediction and detection are very important for improving the effect of treatment and prognosis. Recently, dysregulation and excessive activity of the C4.4A as a member of the LY6/uPAR family of membrane proteins has been shown to associate with multiple cancer types. And previous studies suggest that the C4.4A participates in the invasion and metastasis of NSCLC. At the same time, circumstantial evidence proves that C4.4A and liver kinase B1(LKB1) tumor suppressor gene have a negative regulatory relationship. This article will briefly summarize the recent research progresses of C4.4A in NSCLC.