Abstract: Objective：c-MET gene amplification was regarded as one of the main resistance mechanisms in non-small-cell lung cancer (NSCLC) treated with tyrosine kinase inhibitors (TKIs, gefitinib and erlotinib).The study was to evaluate the difference of c-MET gene amplification between TKI-nave NSCLC cohort and patients resistant to EGFR TKIs. Methods：The baseline group included 55 TKI-na ve NSCLC patients and their tumor specimens were obtained via the lung resection.The resistant group included 23 TKIs resistant patients after first-line TKIs monotherapy.Five tumor samples were collected from the primary cancer via the resection, and nine samples were from metastatic sites via the resection, and the rest were obtained by core needle biopsy of the primary tumors.All the tumor tissues were stored at -80℃ for use.Genomic DNA was extracted from tumor tissues after selection by laser microdissection.Copy numbers of c-MET gene were assessed by quantitative real-time PCR. Results ：c-MET gene amplification was not related to clinicopathologic characteristics both in the baseline group and the resistant group.The prevalence of c-MET amplification in baseline group was 5.5% (3/55), which was lower than the rate in TKIs resistant group (P=0.045, Fisher's exact test).In seven pairs of the tumor samples before and after TKIs treatment, c-MET gene was not amplified in pre-treatment samples, whereas the c-MET gene amplification was found in two cases after TKIs treatment. Conclusion ：Clinicopathologic characteristics may not predict c-MET amplification.In the TKI-nave NSCLC patients, c-MET amplification is accidental.But thegene is amplified in part of NSCLC patients when treated with EGFR TKIs.