The purpose of this study was to assess ADAM17 expression and to explore its contribution to the non-small cell lung cancer (NSCLC). Real-time quantitative reverse transcriptase-polymerase chain reaction was conducted to detect ADAM17 mRNA expression. In addition, ADAM17 expression was analyzed by immunohistochemistry in 124 clinicopathologically characterized NSCLC cases. The correlation of ADAM17 expression with patients' survival rate was assessed by Kaplan-Meier and Cox regression. The expression levels of ADAM17 mRNA and protein in NSCLC tissues were both significantly higher than those in non-cancerous tissues. In addition, high expression of ADAM17 was significantly correlated with tumor grade (P=0.026), tumor size (P=0.001), clinical stage (P=0.016), and lymph node metastases (P<0.001). Furthermore, multivariate analysis suggested that tumor grade, tumor size, clinical stage, lymph node metastases, and ADAM17 expression were independent prognostic indicators for NSCLC. Our data suggest for the first time that the increased expression of ADAM17 in NSCLC is associated significantly with aggressive progression and poor prognosis. ADAM17 may be an important molecular marker for predicting the carcinogenesis, progression, and prognosis of NSCLC.