Abstract: Objective:To investigate the clinicopathological characteristics, chemotherapeutic effect, and prognosis of serum alpha-fe -toprotein (AFP)-producing advanced gastric cancer. Methods:A total of 136 cases of inoperable advanced gastric cancer in our hospi-tal from December 2012to December 2014were included. The relationship between serum AFP with clinicopathological characteris-tics, chemotherapeutic effect, survival, and prognosis were retrospectively analyzed. Results: Among the 136 cases of inoperable ad-vanced gastric cancer, 25cases ( 18. 4%) were of AFP-producing gastric cancer (AFPGC). Compared with the AFP-negative group, AFPGC patients were prone to have disease metastasis to other organs, particularly the liver (56. 0% vs . 19. 8% ,P<0. 001 ), aside from lymph node metastasis (80. 0% vs . 55. 9%,P=0. 026 ). The AFPGC patients had a higher remission rate compared with the AFP-negative group (40. 0% vs . 33. 3% ), whereas the AFP- negative group had a higher disease control rate compared with the AFPGC group (79. 3% vs . 68. 0%). Both had no statistical significance. In the AFP-negative group, median progression-free survival was longer than that of the AF -PGC patients ( 6. 6 monthsvs . 5. 0 months). Meanwhile, one-year survival rate of AFPGC patients was higher than that of AFP-positive group ( 72. 5% vs . 57. 9%). Both had no statistical significance. Median overall survival was longer in the AFP negative group than in the AFPGC group ( 18. 0 monthsvs . 12. 6 months,P=0. 022 ). According to COX model multivariate risk analysis, AFP expression was not an in-dependent risk factor of advanced gastric cancer patients ( P=0. 061 ). In the AFPGC group, patients who underwent chemotherapy with three drugs survived at least 12months or more, whereas those who did not undergo three drug chemotherapy survived less than12 months (P=0. 020 ). Conclusion: Positive serum AFP level was higher in patients with advanced gastric cancer than in those with early-stage gastric cancer. In the AFPGC group, aside from metastasis to the lymph nodes, the disease also metastasized to other organs, par -ticularly the liver. The AFPGC group also had shorter survival time. Nevertheless, chemotherapy with three drugs prolonged their sur -vival time.