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Background: The ARID1A gene encodes adenine-thymine (AT)-rich interactive domain-containing protein 1A, which participates in chromatin remodeling.ARID1A has been showed to function as a tumor suppressor in various cancer types.In the current study, we investigated the expression and prognosis value of ARID1A in primary gastric cancer.Meanwhile, the biological role of ARID1A was further investigated using cell model in vitro.Methodology/Principal findings: To investigate the role of ARID1A gene in primary gastric cancer pathogenesis, real-time quantitative PCR and western blotting were used to examine the ARID1A expression in paired cancerous and noncancerous tissues.Results revealed decreased ARID1A mRNA (P=0.0029) and protein (P=0.0015) expression in most tumor-bearing tissues compared with the matched adjacent non-tumor tissues, and in gastric cancer cell lines.To further investigate the clinicopathological and prognostic roles of ARID1A expression, we performed immunohistochemical analyses of the 224 paraffim-embedded gastric cancer tissue blocks.Data revealed that the loss of ARID1A expression was significantly correlated with T stage (P=0.001) and grade (P=0.006).Consistent with these results, we found that loss of ARID1A expression was significantly correlated with poor survival in gastric cancer patients (P=0.003).Cox regression analyses showed that ARID1A expression was an independent predictor of overall survival (P=0.029).Furthermore, the functions of ARID1A in the proliferation and colony formation of gastric cell lines were analyzed by transfecting cells with full-length ARID1A expression vector or siRNA targeting ARID1A.Restoring ARID1A expression in gastric cancer cells significantly inhibited cell proliferation and colony formation.Silencing ARID1A expression in gastric epithelial cell line significantly enhanced cell growth rate.Conclusions/Significance: Our data suggest that ARID1A may play an important role in gastric cancer and may serve as a valuable prognostic marker and potential target for gene therapy in the treatment of gastric cancer.