Gastric cancer is the most common malignancy in the world. Often diagnosed at advanced and unresectable stage, there is no curative treatment available for gastric cancer. Immunotherapy might be a promising alternative option. The key challenge in gastric cancer diagnosis and immunotherapy is to find an efficient target that not only provide early indication of the disease but also can upregulate the anti-tumor immune response in the cancer patients. Tumor-associated antigens(TAAs) expressed in tumor cells can elicit the immune response in autologous host and are related to changes during the disease process may fulfill this demanding. Now, Thousands of antigens have been discovered by a powerful method called SEREX(serological analysis of tumor antigen by recombinant cDNA expression libraries) and some of SEREX-defined antigens have been evaluated in clinical trails as vaccines for cancer immunotherapy. This review will provide information on the application of SEREX method in gastric cancer research and knowledge learned from these studies to develop antigen-specific diagnosis and therapy for gastric cancer.