Hepatocellular carcinoma (HCC) is a severe neoplastic disease associated with high morbidity and mortality rates. HCC is often detected at advanced stages leading to ineffective curative treatments. Recently, liquid biopsy has emerged as a non-invasive method to identify highly specific HCC biomarkers in bodily fluids such as blood, serum, urine, and saliva. Circulating cell-free nucleic acids (cfNAs), particularly cell-free DNA (cfDNA) and cell-free RNA (cfRNA), have become promising candidates for biomarkers in liquid biopsy applications. While cfDNA presented significant challenges, researchers have turned their attention to cfRNA, which can be efficiently identified through various methods and is considered a potential biomarker for cancer diagnosis and prognosis. This review primarily focuses on studies related to detecting various cfRNA in body fluids as biomarkers. The aim is to provide a summary of available information to assist researchers in their investigations and the development of new diagnostic and prognostic tools.

Department of Histology and Embryology Faculty of Medicine in Pilsen Charles University Alej Svobody 1665 76 Pilsen 323 00 Czech Republic

Laboratory of Cancer Treatment and Tissue Regeneration Biomedical Center Faculty of Medicine in Pilsen Charles University Alej Svobody 1665 76 Pilsen 323 00 Czech Republic; Department of Surgery University Hospital in Pilsen and Faculty of Medicine in Pilsen Charles University Alej Svobody 80 Pilsen 323 00 Czech Republic

Laboratory of Translational Cancer Genomics Biomedical Center Faculty of Medicine in Pilsen Charles University Alej Svobody 1665 76 Pilsen 323 00 Czech Republic

Laboratory of Translational Cancer Genomics Biomedical Center Faculty of Medicine in Pilsen Charles University Alej Svobody 1665 76 Pilsen 323 00 Czech Republic; Department of Cancer Epidemiology German Cancer Research Center Im Neuenheimer Feld 280 Heidelberg 69120 Germany

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