Background: CD44v6 (CD44 variant exon 6) is the chief CD44 variant isoform regulating tumor invasion, progression, and metastasis. The prognostic value of CD44v6 expression in non small cell lung cancer (NSCLC) has been evaluated in many studies, but the results have remained controversial. Thus, we performed a meta-analysis of currently available studies to investigate the prognostic value of CD44v6 expression in NSCLC patients and the relationship between the expression of CD44v6 and clinicopathological features. Materials and Methods: Two independent reviewers searched the relevant literature in Pubmed, Medline and Embase from 1946 to January 2014. Overall survival (OS) and various clinicopathological features were collected from included studies. This meta-analysis was accomplished using STATA 12.0 and Revman 5.2 software. Pooled hazard ratios (HRs) with 95% confidence intervals (95% CIs) were calculated to estimate the effects. Results: A total of 921 NSCLC patients from ten studies met the inclusion criteria. The results showed that CD44v6 high expression was a prognostic factor for poor survival (HR=1.91, 95% CI=1.12-3.26, p<0.05). With respect to clinicopathological features, CD44v6 high expression was related to histopathologic type (squamous cell carcinoma versus adenocarcinoma: OR=2.72, 95% CI=1.38-5.38, p=0.004), and lymph node metastasis (OR=3.02, 95% CI=1.93-4.72, p<0.00001). Conclusions: Our results suggested CD44v6 high expression as a poor prognostic factor for NSCLC, and CD44v6 expression is associated with lymph node metastasis and histopathologic type. Therefore, CD44v6 expression can be used as a novel prognostic marker in NSCLC cases.