Objective To analyze the clinical value of preoperative multislice helice CT (MSCT) combined with serum squamous cell carcinoma (SCC), carbohydrate antigen 19-9 (CA19-9) and carcino-embryonic antigen (CEA) examination in the diagnosis of esophageal cancer. Methods 76 patients with suspected esophageal cancer admitted to the hospital were enrolled. MSCT and serum SCC, CA19-9 and CEA examination were performed before operation. Taking the pathological results as the golden standard, the accuracy, specificity and sensitivity of MSCT and MSCT combined with serum SCC and CA19-9 and CEA examination were compared. Results Pathological examination results showed that there were 68 cases with esophageal cancer and 8 cases without esophageal cancer. The diagnostic sensitivity, specificity, accuracy and the Kappa value of MSCT were 85.29%, 75.00%, 84.21% and 0.42, respectively. The above 4 indexes of MSCT combined with serum SCC, CA19-9 and CEA were 97.06%, 87.50%, 96.05% and 0.80, respectively. The accuracy and sensitivity of MSCT combined with serum SCC, CA19-9 and CEA in the diagnosis of esophageal cancer were significantly higher than those of MSCT (P<0.05). Conclusion Preoperative MSCT combined with serum SCC, CA19-9 and CEA examination can effectively improve the diagnostic sensitivity and accuracy for esophageal cancer, which has relatively higher application value.