Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and a leading cause of cancer-related death globally. In the United States, it is the ninth leading cause of cancer deaths. Despite advances in prevention, screening, and treatment, HCC incidence and mortality continue to rise. Cirrhosis remains the most significant risk factor for HCC, with hepatitis B and C being independent risk factors for cirrhosis. Alcohol consumption is also a major risk factor in the U.S. Diagnosis is confirmed without pathological confirmation, and screening includes radiologic tests like ultrasound, CT, and MRI, as well as serological markers like α-fetoprotein (AFP) every 6 months. Treatment options include orthotopic liver transplantation (OLT), surgical resection, transarterial chemoembolization, radiofrequency ablation, microwave ablation, percutaneous ethanol injection, cryoablation, radiation therapy, systemic chemotherapy, and molecularly targeted therapies. OLT is available for patients meeting Milan or University of San Francisco criteria. Treatment selection depends on tumor size, location, extrahepatic spread, and liver function. HCC is aggressive, often presenting in advanced stages, and can be prevented through measures like hepatitis B vaccination, blood screening, safe injection practices, and antiviral therapy. Continued improvements in surgical and nonsurgical approaches have improved survival. OLT remains the only curative surgical option, but organ shortages limit its use. Sorafenib is a new standard for advanced HCC, improving survival. HCC can be prevented with appropriate measures, and further research is needed to identify better biomarkers for treatment.Hepatocellular carcinoma (HCC) is the most common primary liver malignancy and a leading cause of cancer-related death globally. In the United States, it is the ninth leading cause of cancer deaths. Despite advances in prevention, screening, and treatment, HCC incidence and mortality continue to rise. Cirrhosis remains the most significant risk factor for HCC, with hepatitis B and C being independent risk factors for cirrhosis. Alcohol consumption is also a major risk factor in the U.S. Diagnosis is confirmed without pathological confirmation, and screening includes radiologic tests like ultrasound, CT, and MRI, as well as serological markers like α-fetoprotein (AFP) every 6 months. Treatment options include orthotopic liver transplantation (OLT), surgical resection, transarterial chemoembolization, radiofrequency ablation, microwave ablation, percutaneous ethanol injection, cryoablation, radiation therapy, systemic chemotherapy, and molecularly targeted therapies. OLT is available for patients meeting Milan or University of San Francisco criteria. Treatment selection depends on tumor size, location, extrahepatic spread, and liver function. HCC is aggressive, often presenting in advanced stages, and can be prevented through measures like hepatitis B vaccination, blood screening, safe injection practices, and antiviral therapy. Continued improvements in surgical and nonsurgical approaches have improved survival. OLT remains the only curative surgical option, but organ shortages limit its use. Sorafenib is a new standard for advanced HCC, improving survival. HCC can be prevented with appropriate measures, and further research is needed to identify better biomarkers for treatment.