BACKGROUND: Liver disease is a major cause of mortality and morbidity worldwide and its epidemiology depends on the genetic background, exposure to risk factors, access to healthcare and other sociodemographic characteristics. Brazil is a large country with diverse multicultural and ethnic heritages and important socioeconomic inequalities. The burden of liver disease in Brazil, its regions and population is unknown. METHODS: We retrieved data from the Unified Health System regarding liver diseases and analyzed the mortality and morbidity from 1996 to 2022 by gender, race/ethnicity, age, region and overall. We calculated the age-specific risk of deaths by liver disease, age-standardization of the data, mean hospitalization and liver transplant-associated costs. FINDINGS: Malignant neoplasm of the liver and intrahepatic bile ducts, alcohol-associated liver disease, fibrosis, and cirrhosis of the liver, other diseases of the liver, hepatic failure, chronic viral hepatitis were identified as the major causes of death and morbidity in Brazil in the period analyzed. The epidemiology of these diseases was diverse, with variations according to geographic regions, gender and race/ethnicity. The major economic burden of liver disease is related to liver transplants, a common outcome of the progression of these diseases. INTERPRETATION: Liver disease in Brazil is a serious issue for the public health system due to the high number of deaths and increasing mortality rate. Our study contributes as a necessary prerequisite for the development of tailored public health policies aimed at mitigating the increasing burden of liver diseases in specific populations and regions. FUNDING: CNPq, INCT, CAPES, FAPEMIG.