Objective：This study aims to investigate enhanced CT combined with tumor markers （TM）in diagnosis and prognosis of hepatocellular carcinoma（HCC）. Methods：Total 62 HCC patients were selected and all of them had undergone hepatectomy. In addition，65 healthy subjects were selected as control. Blood samples were collected preoperatively from all subjects，and serum alpha fetoprotein（AFP），carbohydrate antigen 19-9（CA19-9）and carcinoembryonic antigen（CEA）levels were determined by radioimmunoassay. The correlation between serum TM levels and clinicopathological features was investigated by pathological examination. The imaging features of HCC were explored by spiral enhanced CT scanning. The diagnostic effiency of single TM，combined TMs，combined TMs and CT was analyzed by receiver operating characteristic（ROC） curves. Results：The levels of serum AFP，CA19-9 and CEA in HCC patients were significantly higher than those in controls（P < 0.05）. Patients with low differentiation and distant metastasis lesions had higher levels of AFP，CA19-9 and CEA（P < 0.05），compared with patients with high differentiation and no distant metastasis lesions. There were no significant differences in TM levels in HCC patients with different age，gender and clinical stages（P > 0.05）. The ROC analysis showed that the detection of single serum AFP，CEA or CA19-9 had lower specificity and sensitivity compared with the combined detection of three TMs（P < 0.05）. The combined detection of TMs and CT examination could achieve a specificity of 95.71% and a sensitivity of 87.47%，superior to the detection of the TMs（P < 0.05）. Eight HCC patients relapsed within 6 months after operation. Compared with those before operation，the levels of serum AFP，CA19-9 and CEA in the relapsed patients were increased significantly，and the TM levels were higher than those in patients without relapse（P < 0.05）. Conclusion：The detection of serum AFP，CA19-9 and CEA combined with CT can overcome the deficiency of single detection，avoid misdiagnosis，and significantly increase the positive detection rate of HCC。