Cancer is defined by a set of more than 100 diseases that have in common disordered autonomous growth of abnormal cells and genetic alterations, including acquired mutations and genetic instability. The infectious etiology of cancer, on the other hand, is the result of virus activity, which induce tumor cell transformation. This transformation results in activation or deactivation of key regulatory genes, cell proliferation and differentiation. The alterations of these events leads to important modulatory changes in the expression of several proteins and/or their structure, causing profound modifications on cellular metabolism. Carcinomas are cancers that occur in epithelial tissues, as skin or mucous. Among those, the hepatocellular carcinoma (HCC) is one of the most relevant carcinomas and is the sixth most common cancer worldwide. Several factors are associated with progression of HCC, among them diabetes, obesity, metabolic syndrome, alcohol, tobacco, aflatoxins, genetic predisposition and hepatitis B and C virus. The hepatitis C virus (HCV) it is one of the most important etiological agents of HCC, resulting in virus induced liver necroinflammation. The infection of hepatitis C virus (HCV) in hepatocytes is an orchestrated event involving viral oncogenic factors and its development in the host cell, which involve viral envelope glycoprotein structures such as E1 and E2. The most interesting trade is that the HCV genetic material does not invade the nucleus of the infected cell, it acts directly as a mRNA in the cytoplasm, where virus transmission is initiated by the internal ribosome entry site. Numerous events are involved in the molecular pathogenesis of HCC by HVC. In this review, we highlight those involved in p53 signaling pathway; Wnt signaling and E-cadherina/β-catenin activation and TGF-β/activin pathway regulation. As these molecular alterations derived from host-pathogen interactions interfere in hepatocyte normal effectors expression, to understand the interactome behind these well-driven mechanistic events could lead to more realistic molecular targets, as well to early screening for possible biomarkers molecules.