Objective To investigate the effects of pantoprazole treatment in the prevention of gastric tumor bleeding in patients with unresectable gastric cancer. Methods This study was a prospective double-blind,randomized,placebo-controlled trial. From January 2014 to July 2015,patients with gastric tumor bleeding in Xuzhou Cancer Hospital were included in this study. 131 cases of unresectable gastric cancer were randomly divided into two groups. In the experimental group,66 cases were taken pantoprazole 40 mg,1 time / d,and 65 cases in the control group were given placebo 40 mg and 1 time/ d. The course of treatment was 8 weeks. The differences in tumor bleeding,blood transfusion requirements and overall survival time between the two groups were observed during the follow-up period. Results The median follow-up time was 6. 5 ( 3. 3, 13. 2 ) months. Seven cases ( 10. 61%) in pantoprazole group had tumor bleeding, and 13 ( 20%) in the placebo group. There was no significant difference in cumulative risk of tumor bleeding between the two groups (Gray's test: P = 0. 426) . However,in the first 5 months of follow-up,the cumulative incidence of tumor bleeding in pantoprazole group was 0,lower than that in placebo group (9. 23%) (6/ 65) (Gray's test: P = 0. 039). There was no significant difference in blood transfusion requirement and overall survival between the two groups. No drug-related adverse reactions and bleeding related deaths occurred during the follow-up period. Conclusion Pantoprazole can not significantly reduce tumor bleeding in patients with unresectable gastric cancer.