The development and progression of HCC rely on complex molecular mechanisms involving genetic and epigenetic alterations to oncogenes and tumor suppressor genes and disturbed control and inappropriate interaction between important signaling pathways such as Wnt/β-catenin, Hedgehog, MAPK, NOTCH, JAK/STAT3 and PI3K/AKT/mTOR and the circadian clock that leads to metaflammation, disrupted cellular differentiation and growth, finally leading to carcinogenesis [134,135]. Here, CLOCK is linked to hepatocellular carcinoma.