The clinical and prognostic significance of CD133 in non-small-cell lung cancer (NSCLC) remains controversial. To clarify a precise determinant of the clinical significance of CD133, we conducted a systematic review and meta-analysis to evaluate the association of CD133 with prognosis and clinicopathological features of NSCLC patients. The electronic and manual searches were performed through the database of Pubmed, Medline, Web of Science, Scopus, and Chinese CNKI (from January 1, 1982 to January 1, 2014) for titles and abstracts by using the following keywords: "CD133", "ac133" or "Prominin-1", and "lung cancer" to identify the studies eligible for our analysis. Meta-analysis was performed by using Review Manager 5.0 and the outcomes included the overall survival and various clinicopathological features. A total of 23 studies were finally included, and our results showed that CD133 level was significantly correlated with the overall survival (OR = 2.25, 95% CI: 1.24-4.07, P = 0.008) of NSCLC patients but not with the disease free survival (OR = 1.33, 95% CI = 0.77-2.30, P = 0.31). With respect to clinicopathological features, CD133 level was positively correlated with lymph node metastasis (OR = 1.99, 95%CI = 1.06-3.74, P = 0.03), but not correlated with the histological classification (OR = 1.00, 95%CI = 0.81-1.23, P = 0.99(ac), OR = 0.87, 95%CI = 0.61-1.24, P = 0.45(sc)), or differentiation (OR = 0.94, 95%CI 0.53-1.68, Z = 0.20, P = 0.84 random-effect) of NSCLC patients. High level of CD133 expression trends to correlate with a worse prognosis and a higher rate of lymph node metastasis in NSCLC patients, revealing CD133 as a potential pathological prognostic marker for NSCLC patients.