Gastric cancer is highly invasive, aggressively malignant, and amongst the most prevalent of all formsof cancer. Despite improved management strategies, early stage diagnosis of gastric cancer and accurateprognostic assessment is still lacking. Several recent reports have indicated that the pathogenesis of gastriccancer involves complex molecular mechanisms and multiple genetic and epigenetic alterations in oncogenesand tumor suppressor genes. Functional inactivation of the tumor suppressor protein PTEN (Phosphatase andTensin Homolog) has been detected in multiple cases of gastric cancer, and already shown to be closely linkedto the development, progression and prognosis of the disease. Inactivation of PTEN can be attributed to genemutation, loss of heterozygosity, promoter hypermethylation, microRNA- mediated regulation of gene expression,and post-translational phosphorylation. PTEN is also involved in mechanisms regulating tumor resistance tochemotherapy. This review provides a comprehensive analysis of PTEN and its roles in gastric cancer, andemphasizes its potential benefits in early diagnosis and gene therapy-based treatment strategies.