Hepatocellular carcinoma (HCC) is a highly malignant tumor and the third cause of cancer-related death. Serum α-fetoprotein and imaging examination are the most commonly used tests for early diagnosis, treatment and dynamic efficacy monitoring of HCC. However, the accuracy of these approaches is limited and can not clearly reflect the underlying biological characteristics of the tumor. Therefore, novel HCC tumor markers that are more accurate and can comprehensively reflect the biological characteristics of the tumor have potential clinical application value. Circulating tumor cell (CTC), as a kind of cancer cells derived from primary tumors or metastases, provides important information about tumor progression and metastasis, and is good candidate for early diagnosis and evaluation of metastasis, recurrence, and prognosis, and even potential therapeutic target for HCC. This article discusses the application of CTC in the whole clinical course management of HCC patients, as well as its limitations and future research direction.