Objective:The aim of our study was to investigate the clinical significance of Smac (second mitochondria-derived activator of caspase) expression on non-small cell lung cancer (NSCLC). Methods:The expression of Smac was evaluated on RNA and protein level in tumor tissues. The expression of Smac mRNA was examined by RT-PCR in 59 samples of tumor tissues and matched normal lung tissues. The expression of Smac protein was examined by IHC in 213 cancer tissues. Results:The positive rate of Smac mRNA was found in 59.3% of cancer tissues, but only in 30.5% of matched normal tissues (P < 0.05). The positive rate of Smac protein was 76.5%. The expression of Smac in stage II disease was significantly higher than that in stage I disease (P = 0.001). The survival of patients with Smac overexpression was significantly shorter than those who were negative. Conclusion:Smac might be involved in the progression of NSCLC, the biologic significance of Smac in primary lung cancer needs further study.