Hepatocellular carcinoma (HCC) is a liver cancer

highly heterogeneous both at the histopathological and molecular levels. It arises from hepatocytes as the result of the accumulation of numerous genomic alterations in various signaling pathways

including canonical WNT/β-catenin

AKT/mTOR

MAPK pathways as well as signaling associated with telomere maintenance

p53/cell cycle regulation

epigenetic modifiers

and oxidative stress. The role of WNT/β-catenin signaling in liver homeostasis and regeneration is well established

whereas in development and progression of HCC is extensively studied. Herein

we review recent advances in our understanding of how WNT/β-catenin signaling facilitates the HCC development

acquisition of stemness features

metastasis

and resistance to treatment. We outline genetic and epigenetic alterations that lead to activated WNT/β-catenin signaling in HCC. We discuss the pivotal roles of

CTNNB1

mutations

aberrantly expressed non-coding RNAs and complexity of crosstalk between WNT/β-catenin signaling and other signaling pathways as challenging or advantageous aspects of therapy development and molecular stratification of HCC patients for treatment.