OBJECTIVE: To investigate the clinical significance of CD151 expression in non-small cell lung cancer. METHODS: Immunohistochemical staining of SP was applied in the specimens of 78 NSCLC and 22 benign pulmonary diseases to investigate the expression of CD151 protein from January 1st, 2006 to December 31th, 2011 in Yunnan Province Tumor Hospital. The correlation between the expression of CD151 and clinicopathologic features of NSCLC was analyzed. RT-PCR was applied to explore the expression of CD151 mRNA in BEAS-2B, A549, Xuanwei lung adenocarcinoma cell lines XWLC-05 and Gejiu lung squamous carcinoma cell lines YTMLC. RESULTS: The positive rate of CD151 protein in specimens of NSCLC was 57.7%, which was higher than 18.2% of benign pulmonary diseases (χ2=10.72, P=0.001). Overexpression of CD151 protein in NSCLC was not correlated with sex, age, smoking, T-stage, TNM-stage, differentiation and performance status, but was correlated with histology (χ2=6.312, P=0.043) and N-stage (χ2=7.386, P=0.007). Kaplan-Meier survival analysis and log-rank test suggested that overexpression of CD151 protein had poor prognosis. Cox regression suggested CD151 protein expression was independent prognostic factor of NSCLC(P=0.014). Real-time PCR showed the expression of CD151 mRNA was BEAS-2B>A549>XWLC-05>YTMLC. CONCLUSIONS: Overexpression of CD151 protein in NSCLC is correlated with poor prognosis and it can be served as a prognostic factor of NSCLC. There is overexpression of CD151 mRNA in A549 and XWLC-05, which could provide new ideas for the study of pathogenesis, prevention and treatment of lung cancer developed in special environment.