Abstract: Objective To explore the expression of plasma D-dimer in patients with advanced cardia cancer and the effect of disodium cantharidinate and vitamin B6 injection combined with chemotherapy on plasma D-dimer level. Methods Sixty-two advanced cardia cancer patients confirmed by pathological examination were randomly divided into two groups, 31 patients in experimental group (Group A) received PF chemotherapy（4 cycles at least) combined with disodium cantharidinate and vitamin B6 injection (0.5 mg/d), and other 31 patients in control group (Group B) received the same generation chemotherapy but combined with equivalent saline. The D-dimer level was determined one day before the first and third chemotherapy. Results There was no statistical significance of plasma D-dimer level in different gender, age, pathological types or clinical stage in advanced cardia cancer patients before chemotherapy among all groups(P＞0.05). D-dimer level was significantly decreased after chemotherapy(P=0.000), moreover, D-dimer level after chemotherapy in Group A was significantly lower than that in Group B(P=0.042). The ratio of gastrointestinal disorders in Group A (48.4%) was no difference with that in Group B (64.5%) (P=0.200). Moreover, the ratio of blood system disorders in Group A (41.9%) was lower than that in Group B (67.7%, P=0.041). Conclusion After chemotherapy, plasma D-dimer level in advanced cardia cancer patients was significantly decreased. Disodium cantharidinate and vitamin B6 injection could be the co-effective drug with chemotherapy and reduce the adverse events of chemotherapy and the risk of thrombus in advanced cardia cancer patients.