Objective To investigate the relationship between CEA, CA125, CA72-4 and wnt/ β signaling pathway in the serum of patients with gastric cancer and prognosis. Methods Eighty-five cases with gastric cance treated in Dahua Hospital of Shanghai Xuhui District from June 2015 to June 2016 year served as the research objects, the expression of CEA, CA125, CA72-4 and wnt/ β-catenin signaling pathway were detected and their relationship with the chemotherapy effect and clinical prognosis of the patients was examined. Results There was significant differences in CEA, CA-125, CA724, wnt, Tcf-4, β-catenin level among the progression of the disease (PD), stable (SD), partial remission (PR), complete remission (CR) patients (F=28.60, 35.50, 32.40, 33.80, 39.50, 36.50, P<0.05). In addition, the levels in PD patients were significantly higher than those in SD, PR, CR patients.In patients with death, metastasis, recurrence, and stabilization, there was significant differences in CEA, CA-125, CA724, wnt, Tcf-4 and β-catenin level (F=28.60, 35.50, 32.40, 33.80, 39.50, 36.50, P<0.05), Patients with death were significantly higher than those with metastasis, recurrence and stabilizatio.Wnt(P=0.030), Tcf-4(P=0.03), β-catenin(P=0.02)and CA72-4 level(P=0.04) were independent risk factors for death in patients with gastric cancer. Conclusion The expression of CEA, CA125, CA72-4 and wnt/β-catenin signaling pathway in patients with gastric cancer is closely related to the prognosis. Key words: Gastric Cancer; CEA; CA-125; CA72-4; wnt/β-catenin; Prognosis