Primary liver cancer (PLC) is one of the malignant tumors of the digestive system, which poses a huge threat towards human health; hepatocellular carcinoma (HCC) is the major histological type of PLC. 1 Globally, HCC ranks sixth in the number of incidences and second in the mortality rate among all malignancies. 2,3 Moreover, the number of HCC incidences is rising, and it is expected that the annual incidences will be beyond 1 million by 2025. 4,5 Currently, the diagnosis of HCC is mainly based on the detection of serum alpha-fetoprotein (AFP), B-ultrasound, and computed tomography imaging. However, the misdiagnosis and missed diagnosis rates are very high. 6-8 Owing to the insidious onset, poor tumor biological behavior, and rapid progress of HCC, most patients reach advanced stage of the disease and miss the opportunity for radical treatment. Despite the advances in research related to HCC biomarkers, in recent years, lack of specific markers for tumor sub-types, disease stages, or prognosis remains an important gap in the understanding and treatment