Gastric cancer is a major global health threat and is often related with Helicobacter pylori (H. pylori) infection. FRA-1 is a subunit of the activator protein-1 transcription factor complex, which played a central role in cell proliferation and migration. It has also been implicated in stomach inflammation and malignancy. The present study aimed to clarify the relationship between H. pylori infection and production of FRA-1 in controlling cell proliferation and migration and its molecular mechanisms. Cell proliferation was measured by colony formation assay. Cell migration was monitored by transwell migration assay. Gastric mucosal epithelial cells were treated with FRA-1-specific siRNA with or without H. pylori infection in vitro, and RNA and proteins were extracted. The expression of FRA-1 and indicators in cells was determined by RT-PCR and western blot analysis. β-Catenin and TGF-β activities were then assessed by western blotting and immunofluorescence. The expression of FRA-1 increased after H. pylori infection. Additional analysis identified that knockdown of FRA-1 attenuated the H. pylori-induced proliferative activity and migration of gastric cancer cells. Furthermore, upregulation of FRA-1 by H. pylori led to increase in Wnt/β-Catenin levels and TGF-β dependent signaling events. These results demonstrate that the upregulation of FRA-1 in H. pylori-infected gastric epithelial cells plays a key role in the carcinogenic process.