Abstract:  Abstract　Objective: To study the expression of α5β1 integrin and phosphorylated ERK1/2( p-ERK1/2 ) in non-small cell lung cancer ( NSCLC ), and the effect of α5β1 integrin and ERK signal transduction pathway on proliferation and migration of A549 cells. Method: The expression of α5β1 integrin and p-ERK1/2 in 41 specimens of NSCLC, and 15 controled specimens were determined by immunohistochemical assay and Western blot analysis. The correlation between the results of two methods was then analyzed. A549 cells were cultured in vitro, with anti-α5β1 and ERK inhibitor PD98059 as the tool drugs. The proliferation and apoptosis of the A549 cells were measured with the MTT assay and Annexin-V FITC PI double staining, respectively. The protein expression level of MMP-9 was measured with Western blot analysis. The protein expression levels of ERK1/2 were detected by Western blot analysis and the expression levels of ERK1/2 mRNA was measured by RT-PCR. Result: The expression of α5β1 integrin and p-ERK1/2 was significantly higher in NSCLC ( 58.53% and 65.52%, respectively ) compared with that in the normal lung tissue ( 26.67% and 20.00% respectively ). There was also a positive correlation of α5β1 integrin and p-ERK1/2 expression with pathological characteristics ( P = 0.000, P = 0.030 ), lymph node metastasis ( P = 0.014, P = 0.000 ), and clinical stage ( P = 0.027, P = 0.038 ). The expression of α5β1 integrin was positively correlated with p-ERK1/2 expression ( r = 0.375, P < 0.05 ). The anti-α5β1 and ERK inhibitor PD98059 could inhibit the proliferation of A549 cells, resulting in an increase of the percentage in the early apoptotic cells, and down-regulated the expression of MMP-9. In addition, the anti-α5β1 could inhibit the phosphorylated ratio of ERK by down-regulating the expression of ERK mRNA and the relative proteins. Conclusion: The positive rates of α5β1 integrin and p-ERK1/2 are higher in NSCLC than in the normal lung tissue. Anti-α5β1 can down-regulate the expression of ERK mRNA and the phosphorylated ratio, and can inhibit the proliferation of A549 cells and down-regulate the expression of MMP-9. This indicates that the α5β1 integrin-mediated ERK signal transduction pathway might lead to the abnormal proliferation and migration of A549 cells.