Abstract: Objective To assess the value of detecting peripheral blood circulating tumor cells (CTCs) in the diagnosis and treatment of hepatocellular carcinoma (HCC). Methods A total of 296 patients diagnosed with HCC admitted in our department from July 2013 to January 2015 were analyzed, with 39 patients with benign liver disease serving as the control group. The distribution of CTCs in the peripheral blood of HCC patients were detected by CanPatrolTM CTCs, and its relationship with the clinical features and prognosis of the patients were analyzed. Results CTCs were detected in 64.5% (191/ 296) of the HCC patients but in none of the control group (P<0.05). Positive CTCs in peripheral blood of HCC patients were significantly correlated with serum AFP level, tumor number, TNM stage, BCLC stage, portal vein tumor thrombus and metastasis (P<0.05). In 127 HCC patients receiving radical surgery, the patients positive for CTCs showed significantly shorter relapse-free survival time (P<0.05). Conclusion Positive CTCs in the peripheral blood may indicate a poor prognosis in HCC patients. CTCs may serve as a indicator for monitoring the prognosis of HCC.