Hepatitis C virus (HCV) is a principal cause of liver-related mortality worldwide. Recent estimates have shown an increase in its prevalence over the last decade to 2.8%, with approximately 185 million infections worldwide. HCV was considered as oncogenic to humans by the International Agency for Research on Cancer (IARC) in 1993. Four HCV proteins (core, NS3, NS5A and NS5B) appear to deregulate potentially oncogenic signaling pathways. Proliferative signaling pathways of mammalian cells are altered by extracellular factors that incorporate specific programs of gene transcription and protein regulation. Physiological feedback systems like contact inhibition, controlled availability of growth factors and others ensure a firm regulation of the proliferative signaling pathways. Uncontrolled cell proliferation is the principal aspect of most cancer types. The dedifferentiation of hepatocytes, which is accompanied by significant changes in intracellular communication and nutrient supply, is a key aspect of HCC development. The current understanding of tumor formation has greatly benefited from the discovery and study of stem cell-like cells in cancers. NF-κB participates in the immune system’s role in the removal of transformed cells. This is supported by the finding that NF-κB activation during the acute inflammatory response is strongly correlated with the response of cytotoxic immune cells. Once phosphorylated, STAT3 joins forces with STAT1 or STAT5 to form homo- or heterodimers that move to the nucleus and bind particular DNA sequences. Without a doubt, STAT3 transcriptional activity depends on phosphorylation. However, unphosphorylated STAT3 also performs biological activities like regulating the expression of genes involved in cell cycle progression.