Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers globally, with limited therapeutic options and a poor prognosis. The article reviews the current understanding of HCC pathogenesis, highlighting the complex interplay between genetic, environmental, and cellular factors. HCC is primarily driven by chronic liver diseases such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, alcohol consumption, and exposure to aflatoxin B1. These factors contribute to liver cirrhosis, a key precursor to HCC, through mechanisms like inflammation, oxidative stress, and genomic instability. HBV and HCV induce hepatocarcinogenesis through viral integration, immune responses, and activation of oncogenic pathways, while alcohol and aflatoxin B1 primarily act through oxidative stress and mutagenic effects. Genetic alterations, including mutations in p53, β-catenin, and overexpression of ErbB and MET receptors, are common in HCC. Epigenetic changes, such as DNA methylation, also play a role. Genomic instability, characterized by telomere shortening and chromosomal abnormalities, is a hallmark of HCC. Despite advances, challenges remain in understanding the molecular mechanisms, identifying early biomarkers, and developing effective therapies. Future research should focus on comprehensive genomic analyses, comparative studies with animal models, and the development of targeted treatments to improve outcomes for HCC patients.Hepatocellular carcinoma (HCC) is one of the most lethal and prevalent cancers globally, with limited therapeutic options and a poor prognosis. The article reviews the current understanding of HCC pathogenesis, highlighting the complex interplay between genetic, environmental, and cellular factors. HCC is primarily driven by chronic liver diseases such as hepatitis B virus (HBV) and hepatitis C virus (HCV) infections, alcohol consumption, and exposure to aflatoxin B1. These factors contribute to liver cirrhosis, a key precursor to HCC, through mechanisms like inflammation, oxidative stress, and genomic instability. HBV and HCV induce hepatocarcinogenesis through viral integration, immune responses, and activation of oncogenic pathways, while alcohol and aflatoxin B1 primarily act through oxidative stress and mutagenic effects. Genetic alterations, including mutations in p53, β-catenin, and overexpression of ErbB and MET receptors, are common in HCC. Epigenetic changes, such as DNA methylation, also play a role. Genomic instability, characterized by telomere shortening and chromosomal abnormalities, is a hallmark of HCC. Despite advances, challenges remain in understanding the molecular mechanisms, identifying early biomarkers, and developing effective therapies. Future research should focus on comprehensive genomic analyses, comparative studies with animal models, and the development of targeted treatments to improve outcomes for HCC patients.