ABSTRACT: BACKGROUND AND OBJECTIVE: The prognosis varied among the patients with the same stage, therefore there was a need for new prognostic and predictive factors. The aim of this study was to evaluate the relationship of apoptosis-related biological markers such as p53, bcl-2, bax, and c-myc, and clinicopathological features and their prognostic value. METHODS: From 1996 to 2007, 4426 patients had undergone curative D2 gastrectomy for gastric cancer at Fudan University Shanghai Cancer Center. Among 501 patients, the expression levels of p53, bcl-2, bax, and c-myc were examined by immunohistochemistry. The prognostic value of biological markers and the correlation between biological markers and other clinicopathological factors were investigated. RESULTS: There were 339 males and 162 females with a mean age of 57. The percentages of positive expression of p53, bcl-2, bax, and c-myc were 65%, 22%, 43%, and 58%, respectively. There was a strong correlation between p53, bax, and c-myc expression (P=0.00). There was significant association between bcl-2, and bax expression (P<0.05). p53 expression correlated with histological grade (P=0.01); bcl-2 expression with pathological stage (P=0.00); bax expression with male (P=0.02), histological grade (P=0.01), Borrmann type (P=0.01), tumor location (P=0.00), lymph node metastasis (P=0.03), and pathological stage (P=0.03); c-myc expression with Borrmann type (P=0.00). bcl-2 expression was related with good survival in univariate analysis (P=0.01). Multivariate analysis showed that bcl-2 expression and pathological stage were defined as independent prognostic factors. There were significant differences of overall 5-year survival rates according to bcl-2 expression or not in stage IIB (P=0.03). CONCLUSION: The expression of bcl-2 was an independent prognostic factor for patients with gastric cancer; it might be a candidate for the gastric cancer staging system.