Liver cancer is a major cause of cancer-related deaths worldwide, surpassing other forms of cancer in terms of mortality rates. Liver cancer encompasses various aggressive tumor types, including hepatocellular carcinoma (HCC) and intrahepatic cholangiocarcinoma (iCCA), as well as rare forms such as fibrolamellar carcinoma and hepatoblastoma. The incidence and mortality rates of iCCA are also rising globally, with variations among different racial and ethnic groups. Chronic liver damage plays a central role in the development of both HCC and iCCA, creating a pro-oncogenic state that facilitates the transformation of cells and the progression of liver cancer. Extensive research has revealed the genetic complexity of liver cancer, with frequent somatic mutations observed in genes such as TP53, MYC, and WNT/beta-catenin pathway-related genes. Mutations in the promoter region of the telomerase gene (TERT) have also emerged as a predominant mechanism activating telomerase and are detected in a significant proportion of hepatocellular carcinomas. Epigenetic modifications, including DNA methylation and histone modifications, contribute to liver cancer development and progression. This review aims to consolidate the current understanding of liver cancer biology, focusing on genetic alterations, tumor heterogeneity, and the role of key cellular players in tumor initiation and perpetuation. By integrating these multifaceted aspects, a comprehensive understanding of liver cancer can be achieved, leading to improved strategies for combating this challenging disease.