Our study revealed that serum NY‐ESO‐1 and p53 antibodies were positive in 12.6% and 18.1% of patients with gastric cancer, respectively, and the combination of NY‐ESO‐1 and p53 antibody responses to general tumor markers CEA and CA19‐9 increased the diagnostic accuracy of gastric cancer. The gene discussed is TP53; the disease is gastric cancer.