Gastric cancer is a considerable health issue worldwide and remains a major challenge for the oncology community. The phosphatidylinositol-3 kinase (PI3K) signaling pathway is constitutively activated and/or upregulated in various malignancies and activation of this pathway plays a critical role in tumour progression. Alterations of PI3K pathway in gastric cancer and its correlations to clinicopathologic features were investigated followed by exploration of PI3K targeted cancer therapy in vitro. It was shown that PI3K pathway alterations occur frequently in gastric carcinoma. PI3K inhibitor (LY294002) was demonstrated to be sensitive in certain types of gastric cancer cell lines as well as have synergistic effect with conventional cytotoxic agents (5-FU and Oxaliplatin).