Abstract: Objective To explore the effect of 5-aza-2-deoxycytidine(5-Aza-CdR) on the proliferation of non-small cell lung cancer cell line A549 and the expression of tissue factor pathway inhibitor 2 (TFPI-2) gene mRNA, and to explore whether 5-Aza-CdR could inhibit the invasion capacity of NSCLC A549 cell via TFPI-2 gene. Methods A549 cells were treated with 5-Aza-CdR at different concentrations. The proliferation of A549 cells was detected by MTT assay after treatment for 24 h, 48 h and 72 h, respectively. Cell cycle of A549 cells were analyzed by fl ow cytometer(FCM) after treatment for 72 h. The expression of TFPI-2 gene mRNA was detected by real time polymerase chain reaction(real-time PCR) after treatment for 72 h, and invasion capacity of A549 cells was detected by Transwell assay after treatment for 24 h. Results MTT showed that A549 cell growth had been restrained after treatment at different concentrations for 24 h, 48 h and 72 h, respectively, in an obvious dose- and time-dependence manner. FCM and real-time PCR showed that after treatment at the concentration of 0, 1, 5, 10 μM for 72 h respectively, proliferation indexes of A549 cells were (30.43±0.99)%, (23.89±0.83)%, (16.19±0.34)%, (6.49±0.55)%(P<0.05), and relative mRNA expression levels of TFPI-2 gene were (1±0), (1.49±0.14), (1.86±0.09), (5.80±0.15)(P<0.05), and TFPI-2 gene mRNA expression had increased along with the increasing concentration of 5-Aza-CdR. Transwell small chamber assay showed that the average numbers of cells passed the membrane was (316.15±18.7), (84.15±12.14), (28.85±7.13) and (14.35±3.33) at the concentration of 0, 1, 5, 10 μM respectively(P<0.05). Conclusion 5-Aza-CdR could restore TFPI-2 gene expression in NSCLC cell line A549 cells and restrain the proliferation and invasion capacity of A549 cells by reducing TFPI-2 gene methylation.