〔Abstract〕 Objective To analyze the effects of transglutaminase 2(TGM2) gene interference on the malignant proliferation and movement of lung cancer cells. Methods A549 cells in logarithmic growth phase were divided into control group, shRNA-NC group and TGM2-shRNA1 group. After transfection, expression levels of TGM2 mRNA and protein after transfection were detected by RT-PCR and Western blot. The growth of A549 cells was detected by clone formation assay. The proliferation activity of cells was detected by CCK-8. The apoptosis rate was detected by flow cytometer. The invasion of cells was detected by Transwell. The number of tubule formation in each group was observed under microscope. The expression of E-cadherin(E-cad), N-cadherin(N-cad), fibronectin(FN) and vascular endothelial growth factor(VEGF) in each group was detected by Western blot. Results Compared with shRNA-NC group, the mRNA level and protein expression of TGM2 in TGM2-shRNA1 group were decreased(P<0.05), and the rate of clone formation, proliferation activity, number of invasive cells and number of tubules formation were decreased(P<0.05).The apoptosis rate and the expression of E-cad protein were increased(P<0.05), while the expression of N-cad, FN and VEGF protein were decreased(P<0.05). Conclusion TGM2 gene silencing can inhibit the expression of VEGF protein, inhibit the malignant proliferation and invasion of A549 cells, and promote apoptosis.