【Abstract】 Objective The relevant research has indicated that chemokine receptor 4 (CXCR4) closely related to tumor development. It can promote cell growth and inhibit apoptosis and other important functions, and has been confirmed can promote metastasis in a variety of tumors. Peptide peptidase IV (DPP IV), also known as CD26, is involved in protein hydrolysis, cell adhesion, immune response, regulation of apoptosis, and plays an important role in tumor invasion and metastasis. The purpose of this study was to analyze the expression characteristics of CXCR4 and CD26 in the invasive adenocarcincoma of the lung and lymph node metastases, and to investigate the relationship between the expression of CXCR4 and CD26 and the clinicopathological features and prognosis of invasive adenocarcincoma of the lung. Methods The tissue chip and immunohistochemistry techniques were used to detect the expression of CXCR4 and CD26 in 57 cases of normal lung tissues, 222 cases of the primary lesion of invasive adenocarcinoma of the lung and 54 cases of corresponding lymph node metastases. Results The expression of CXCR4 in adjacent normal lung tissues, the primary lesion of the invasive adenocarcinoma of the lung, and lymph node metastases was gradually increased (P＜0.05), and the expression of CD26 in adjacent normal lung tissues, the primary tumor of the invasive adenocarcinoma of the lung, and lymph node metastases appeared upward tendency (P＜0.05). In addition, the expression level of CXCR4 in the primary lesion was relevant to morphological grading, metastases and TNM staging of invasive adenocarcinoma of the lung （P＜0.05）, as well as the expression level of CD26 in the primary lesion was correlated with morphological grading and the tumor size of invasive adenocarcinoma of the lung（P＜0.05）. KaplanMeier survival analysis relevant that gender, age, tumor size, morphological grading, metastasis, TNM staging were correlated with the postoperative survival rate of invasive adenocarcinoma of the lung patients (P＜0.05). The Cox regression model was used to determine gender, age, morphological grading, tumor size, metastasis and TNM staging were independent prognostic factors of invasive adenocarcinoma of the lung(P＜0.05). Spearman correlation analysis showed that the expression of CXCR4 and CD26 in invasive adenocarcinoma of the lung was positively correlated with independent prognostic factors of invasive adenocarcinoma of the lung(r＞0，P＜0.05). Conclusion CXCR4 and CD26 may play important roles in invasion and metastasis in invasive adenocarcinoma of the lung, so these tow marker can be employed to evaluate the prognosis of the invasive adenocarcinoma of the lung patients.