The majority of the human genome comprises of DNA genes that are translated into RNAs but not into proteins. These RNA molecules are named non‐coding RNAs (ncRNA). While in the past it was thought that ncRNAs would be redundant without relevant functions, it is now well established that ncRNAs identify a class of regulatory molecules that finely tune cell homeostasis and are deregulated in disease states, including Hepatocellular Carcinoma (HCC). Of note, the number of ncRNAs within a cell increases progressively with the complexity of the species indicating their essential role in the maintenance of regulatory networks that impact the intricacy of the organism. ncRNAs have been demonstrated to mediate HCC development and progression by affecting intrinsic cancer cell signaling and cross talk between malignant cells and the microenvironment. They hold promise as clinical biomarkers, but further evidence is warranted prior to translation and integration within clinical practice
