OBJECTIVE To analyze the clinicopathologic features and prognosis of α-fetoprotein (AFP)-producing gastric cancers (AFPGC). METHODS Fifty-one serum AFP-positive patients with positive immunohistochemical staining of AFP in the primary lesions (study group) and sixty-five gastric cancer cases with normal AFP level (control group) treated in our department from January 2005 to December 2007 were included in this study. Their clinicopathologic features and follow-up data were statistically analyzed. RESULTS Compared with the control group, the study group had a higher incidence of poorly differentiated adenocarcinoma (P=0.021) and liver metastasis (P=0.001) than that in the control group.The TNM stages in the study group were significantly higher than those in the control group (P=0.001). The 1-, 2-, and 5-year survival rates of the study group were 62.7%, 27.5% and 4.7%, respectively, and the median survival was 16 months, significantly lower than the 84.6%, 55.4%, 16.5%, and 30 months of the control group (P<0.001 for all). The serum AFP levels in the study group ranged from 58.63 µg/L to 12 100.00 µg/L, and could be classified into two groups:27 cases <500 µg/L, and 24 cases ≥500 µg/L. There was no significant difference of the immunohistochemical staining results between the two subgroups (P=0.912). CONCLUSIONS AFPGC is a special type of gastric cancer with high degree of malignancy and poor prognosis. Monitoring of serum AFP level can earlier detect the progression of disease and give corresponding treatment.