Background: Hepatocellular carcinoma (HCC) represents the most common malignant liver tumor in humans, which incidence and mortality have increased in Europe and United States in the last years. Most patients are diagnosed at an advanced stage, when it is not amenable to curative therapies, so there is an urgent need for new, more effective therapeutic tools and strategies. The molecular mechanisms of hepatocarinogenesis and HCC progression have been increasingly understood with intense research in recent years.Methods: The goal of this work is to discuss the different signalling pathways as important potential therapeutic targets. Results: Disruption of pathways known to play roles in HCC, such as Wnt/β-catenin, Hedgehog, RAF/MEK/ERK, tryosine kinase receptor-related pathway, Met-HGF, VEGF/ VEGF and ROR signalling pathways may be seminal for liver oncogenesis. Conclusion: This review reveals that oncogenes, especially microRNAs that are conserved across species and interfere with signalling pathways might be used as promising strategies for halting or reversing the progression of HCC.