To evaluate the value of combined detection of serum CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA andTPS for the clinical diagnosis of upper gastrointestinal tract (GIT) cancer and to analyze the efficacy of thesetumor markers (TMs) in evaluating curative effects and prognosis. A total of 573 patients with upper GIT cancerbetween January 2004 and December 2007 were enrolled in this study. Serum levels of CEA, CA19-9, CA24-2,AFP, CA72-4, SCC, TPA and TPS were examined preoperatively and every 3 months postoperatively by ELISA.The sensitivity of CEA, CA19-9, CA24-2, AFP, CA72-4, SCC, TPA and TPS were 26.8%, 36.2%, 42.9%, 2.84%,25.4%, 34.6%, 34.2% and 30.9%, respectively. The combined detection of CEA+CA199+CA242+CA724 hadhigher sensitivity and specificity in gastric cancer (GC) and cardiac cancer, while CEA+CA199+CA242+SCCwas the best combination of diagnosis for esophageal cancer (EC). Elevation of preoperative CEA, CA19-9 andCA24-2, SCC and CA72-4 was significantly associated with pathological types (p<0.05) and TNM staging (p<0.05).Correlation analysis showed that CA24-2 was significantly correlated with CA19-9 (r=0.810, p<0.001). The levelsof CEA, CA19-9, CA24-2, CA72-4 and SCC decreased obviously 3 months after operations. When metastasisand recurrence occurred, the levels of TMs significantly increased. On multivariate analysis, high preoperativeCA72-4, CA24-2 and SCC served as prognostic factors for cardiac carcinoma, GC and EC, respectively. combineddetection of CEA+CA199+CA242+SCC proved to be the most economic and practical strategy in diagnosis of EC;CEA+CA199+CA242+CA724 proved to be a better evaluation indicator for cardiac cancer and GC. CEA andCA19-9, CA24-2, CA72-4 and SCC, examined postoperatively during follow-up, were useful to find early tumorrecurrence and metastasis, and evaluate prognosis. AFP, TPA and TPS have no significant value in diagnosis ofpatients with upper GIT cancer.