PURPOSE: The prognostic value of aberrant C-X-C chemokine receptor type 4 (CXCR4) levels in NSCLC has been described in empirical studies. This meta-analysis evaluates the value of CXCR4 as a prognostic marker for NSCLC and determines the relationship between CXCR4 and clinicopathological features of NSCLC. METHODS: A comprehensive search of the English-language literature in PubMed, Embase, Google Scholar and Web of Science was performed. Articles containing sufficient published data to determine an estimate of the hazard ratio (HR) and a 95% confidence interval (95% CI) for over survival (OS) or disease-free survival (DFS) were selected. Of 417 potentially relevant studies, 10 eligible studies (1,334 NSCLC patients) met the inclusion criteria. RESULTS: Overall, high CXCR4 expression was significantly associated with a poor OS rate (HR=1.59, 95% CI=1.36-1.87, P < 0.001) while the association with DFS was not statistically significant (HR=1.00, 95% CI=0.37-2.69, P=0.993). Stratified analysis by subcellular localization found that CXCR4 overexpression in the non-nucleus predicts poor OS (HR=1.65, 95% CI=1.40-1.95, P < 0.001) and DFS (HR=3.06, 95% CI=2.15-4.37, P < 0.001), but elevated CXCR4 expression in the nucleus was positively associated with DFS (HR=0.44, 95% CI=0.26-0.75, P=0.002). NSCLC patients with CXCR4 expression were more likely to be diagnosed with adenocarcinoma cancer (OR=1.45, 95% CI=1.07-1.95, P=0.016), lymph node involvement (OR=0.69, 95% CI=0.50-0.96, P=0.027), and distant metastasis (OR=0.36, 95% CI=0.14-0.93, P=0.035). CONCLUSION: Aberrant overexpression of CXCR4 is associated with worse overall survival, adenocarcinoma histology, distant metastasis, lymph node involvement in NSCLC.