On the global scale, primary liver cancer (PLC) is the second leading cause of death due to cancer in men, and the third most prevalent cause of death in both sexes. Hepatocellular carcinoma (HCC) accounts for almost 75% of the total cases among primary liver malignancies. Curative operations for HCC include liver resection, ablation, and transplantation. However, a timely diagnosis is required for these operations to be successful. Hepatocarcinogenesis is a multistep process and can be induced by molecular alterations at both the genetic and epigenetic levels. The characteristic pathogenesis mechanisms of HCC are abnormal signal transduction resulting in uncontrolled cell proliferation, loss of apoptosis or programmed cell death, tissue invasion and metastasis allowing the spread of cancer, and finally angiogenesis which leads to the enhanced blood supply of tumors. In addition to epigenetic control of tumorigenesis. The p53 cell-cycle pathway, mutations in oxidative stress pathways, PI3K/AKT/mTOR, and Ras/Raf/MAPK signaling pathways are of great important pathways in HCC pathogenesis. Crosstalk between these pathways may be targeted by anti-cancer medications.