Abstract: Objective To investigate the effect of Helicobacter pylori infection on the malignant transformation of gastric cancer cell lines and to explore its possible mechanism. Methods The gastric cancer AGS cells were divided into cytotoxin related gene A (CagA) plasmid group (transfected with pCDNA3.1-CagA plasmid) and negative control group (transfected with pCDNA3.1 blank plasmid), and were divided into CagA plasmid group (transfected with PCDNA3.1-CagA plasmid and pEGFP-C1-PDCD4 plasmid),the CagA+programmed cell death factor 4 (PDCD4) plasmid group (transfected with pCDNA3.1-CagA plasmid and pEGFP-C1-PDCD4 plasmid) and Negative control group (transfected with pCDNA3.1 blank plasmid and pEGFP-C1 blank plasmid). The levels of PDCD4, Twist1, E-cadherin, Vimentin mRNA in cells were measured by reverse transcription-polymerase chain reaction (RT-PCR). The protein levels of PDCD4, Twist1, E-cadherin and Vimentin were determined by Western blot, cell invasion was measured using transwell chamber. Results The expression of Twist1 mRNA and Vimentin mRNA in CagA plasmid group were higher than those in negative control group (P<0.05). The expression of PDCD4 mRNA and E-cadherin mRNA in CagA plasmid group were lower than those of negative control group (P<0.05). The expression of Twist1 mRNA and Vimentin mRNA in CagA+PDCD4 plasmid group were lower than those in CagA plasmid group (P<0.05). The expression of PDCD4 mRNA and E-cadherin mRNA in CagA+PDCD4 plasmid group were higher than those of CagA plasmid group (P<0.05). The expression of Twist1 protein and Vimentin protein in CagA plasmid group were higher than those in negative control group (P<0.05). The expression of PDCD4 protein and E-cadherin protein in CagA plasmid group were lower than those of negative control group (P<0.05). The expression of Twist1 protein and Vimentin protein in CagA + PDCD4 plasmid group were lower than those in CagA plasmid group (P<0.05). The PDCD4 protein and E-cadherin protein in CagA+PDCD4 plasmid group were higher than those of CagA plasmid group (P<0.05). The number of invasive cells in CagA plasmid group was higher than that in negative control group (P<0.05). The number of invasive cells in CagA+PDCD4 plasmid group was lower than that in CagA plasmid group (P<0.05). Conclusion Helicobacter pylori infection can increase the invasion of gastric cancer cells. The mechanism may be that Helicobacter pylori independent factor CagA promotes the epithelial-mesenchymal transition of gastric cancer cells by inhibiting PDCD4 expression.