Objective: Annexin a2 (ANXA2) has been reported to be involved in various biologic processes. However, the clinical significance and biological role of ANXA2 in gastric cancer remains unclear. Methods: ANXA2 protein expression was quantified in gastric cancer tissues and adjacent normal tissues by immunohistochemical staining. Expressions of ANXA2 in four human gastric cancer cell lines with different grade of differentiation (SGC-7901, MKN-45, BGC-823 and AGS) were analyzed by quantitative real time PCR and western blotting. ANXA2 expression was silenced by LV-ANXA2- RNAi in AGS cells. MTT and colony formation tests were used to analysis the cell proliferation of cells. Cell apoptosis and cell cycle assays using flow cytometry were measured to evaluate the death of cells. Migration and invasion were measured with wound healing test, transwell and matrigel invasion chambe assays. Then, mRNA microarray expression profiles were carried out and the function of ANXA2 silencing on the expression of c-met and RAP1A was elucidated by western blot analysis. Results: Compared with adjacent normal tissue, ANXA2 is upregulated in human gastric tissues and is associated with the clinical features of gastric cancer. ANXA2 is high expressed in four human gastric cancer cells. AGS cells displayed the highest ANXA2 expression among the four kinds of human gastric cancer cell lines and were selected as a cell model for further experiments. Levels of ANXA2 expression was significantly declined in AGS cells infected with LV-ANXA2-RNAi. Silencing of ANXA2 led to reduced cell proliferation and increased death of AGS cells, through down regulation of c-met, and led to clear reduction in AGS cell migration and invasion via down regulation of RAP1A. Conclusion: Our finding shows that overexpression of ANXA2 is correlated with high clinical stage and poor overall survival in patients with gastric cancer. ANXA2 silencing suppresses the proliferation, enhances the death and contributes to the motility gastric cancer cells.