Hepatocellular carcinoma (HCC) is a major global health issue, with risk factors including chronic hepatitis C (HCV) and B (HBV) infections, alcohol use, non-alcoholic fatty liver disease (NAFLD), and diabetes. The incidence of HCC has been rising in North America and parts of Europe, while declining in traditionally high-risk regions like Japan and parts of China. In the United States, HCC incidence rates in Hispanics have surpassed those in Asians, with higher rates among US-born Hispanics compared to foreign-born ones. HCV and HBV remain the leading causes of HCC globally, with HCV being the most prevalent in the US. Advances in HCV treatment, such as direct-acting antivirals (DAAs), have significantly reduced HCC risk in treated patients, though the magnitude of this reduction depends on treatment access and adherence. Similarly, nucleos(t)ide analogues (NAs) for HBV have reduced HCC risk, but not eliminated it. NA treatment is associated with a reduced HCC risk, but the effectiveness varies based on factors like cirrhosis, age, and viral load. NA-based scoring systems, such as the CAMD score, are used to predict HCC risk in patients on NA therapy. NAFLD is now the leading cause of chronic liver disease worldwide, with a significant contribution to HCC. NAFLD-related HCC is the fastest-growing cause of HCC-related liver transplants in the US, though the exact risk factors and progression are not fully understood. HCC risk is also influenced by diabetes and obesity, with type 2 diabetes associated with a 2-3 fold increased risk of HCC. Obesity is linked to a higher risk of HCC, with a higher waist-to-hip ratio associated with increased risk. Population attributable fraction (PAF) analysis shows that NAFLD is a more common but weaker risk factor for HCC compared to HCV and HBV. HCC diagnosis relies on imaging and biopsy, with the AASLD criteria and LIRADS system being widely used. HCC prognosis is complex, with factors like tumor burden, liver function, and performance status influencing survival. The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely used for HCC staging. HCC treatment options vary based on tumor size, stage, and patient characteristics. Liver transplantation is the best option for curative treatment, but access is limited by the Milan criteria. Advances in treatment include combination therapies like TACE + RFA, TACE + tyrosine-kinase inhibitors (TKIs), and radioembolization. Immunotherapy is being explored in combination with local treatments for advanced HCC. Overall, HCC management requires a multidisciplinary approach, with surveillance, early detection, and tailored treatment strategies to improve outcomes.Hepatocellular carcinoma (HCC) is a major global health issue, with risk factors including chronic hepatitis C (HCV) and B (HBV) infections, alcohol use, non-alcoholic fatty liver disease (NAFLD), and diabetes. The incidence of HCC has been rising in North America and parts of Europe, while declining in traditionally high-risk regions like Japan and parts of China. In the United States, HCC incidence rates in Hispanics have surpassed those in Asians, with higher rates among US-born Hispanics compared to foreign-born ones. HCV and HBV remain the leading causes of HCC globally, with HCV being the most prevalent in the US. Advances in HCV treatment, such as direct-acting antivirals (DAAs), have significantly reduced HCC risk in treated patients, though the magnitude of this reduction depends on treatment access and adherence. Similarly, nucleos(t)ide analogues (NAs) for HBV have reduced HCC risk, but not eliminated it. NA treatment is associated with a reduced HCC risk, but the effectiveness varies based on factors like cirrhosis, age, and viral load. NA-based scoring systems, such as the CAMD score, are used to predict HCC risk in patients on NA therapy. NAFLD is now the leading cause of chronic liver disease worldwide, with a significant contribution to HCC. NAFLD-related HCC is the fastest-growing cause of HCC-related liver transplants in the US, though the exact risk factors and progression are not fully understood. HCC risk is also influenced by diabetes and obesity, with type 2 diabetes associated with a 2-3 fold increased risk of HCC. Obesity is linked to a higher risk of HCC, with a higher waist-to-hip ratio associated with increased risk. Population attributable fraction (PAF) analysis shows that NAFLD is a more common but weaker risk factor for HCC compared to HCV and HBV. HCC diagnosis relies on imaging and biopsy, with the AASLD criteria and LIRADS system being widely used. HCC prognosis is complex, with factors like tumor burden, liver function, and performance status influencing survival. The Barcelona Clinic Liver Cancer (BCLC) staging system is the most widely used for HCC staging. HCC treatment options vary based on tumor size, stage, and patient characteristics. Liver transplantation is the best option for curative treatment, but access is limited by the Milan criteria. Advances in treatment include combination therapies like TACE + RFA, TACE + tyrosine-kinase inhibitors (TKIs), and radioembolization. Immunotherapy is being explored in combination with local treatments for advanced HCC. Overall, HCC management requires a multidisciplinary approach, with surveillance, early detection, and tailored treatment strategies to improve outcomes.