Abstract: Objective To explore the predictive value of serum pepsinogen in the prognosis of patients with gastric cancer. Methods A total of 118 patients with gastric cancer admitted to the People's Hospital of Hanzhong and Hanzhong Central Hospital from January 2015 to September 2016 were retrospectively collected. The serum levels of pepsinogen, carbohydrate antigen 199 (CA199) and carcinoembryonic antigen (CEA) were measured on admission. After radical gastrectomy and chemotherapy, the patients were followed up for 2 years. The predictive value of serum pepsinogen, CA199 and CEA on the death of gastric cancer patients within 5 years were observed. Results When compared with the survivors, CA199 was significantly increased in patients who died (48.43±17.04) U/ml vs. (36.71±15.78) U/ml, P=0.000; CEA was significantly increased (53.97±22.12) μg/L vs. (41.62±11.54) μg/L, P=0.000; pepsinogen I was significantly decreased (30.55±5.74) μg/L vs. (44.00±8.44) μg/L, P=0.000; and pepsinogen Ⅱ was significantly increased (19.09±5.81)μg/L vs. (16.16±5.11) μg/L, P=0.005. PepsinogenⅠ, pepsinogen Ⅱ, CA199 and CEA had some values in predicting the death of gastric cancer patients within 2 years, but pepsinogen Ⅰ had the highest value 95% CI, 0.094 (0.042-0.147), P=0.000. Conclusions The pepsinogenⅠ has a higher predictive value for the prognosis of patients with gastric cancer, and is worthy of promotion.