AbstractReal‐world evidence includes all health‐related information, such as electronic health records, insurance claims, pharmacy records and wearables that are obtained outside of clinical trials. These data can provide critical insights into the natural history of disease and evaluate the safety and effectiveness of treatment regimens used in clinical practice. Real‐world data have been applied to varying degrees by global regulatory agencies to inform and expedite many phases of drug development and help refine the use of therapeutic regimens after marketing, especially in populations that are under‐represented in registration trials. For the management of hepatocellular carcinoma, early detection provides the best chance for curative therapies, whose success has been evaluated in numerous cohorts. The availability of novel systemic therapies, including kinase inhibitors and immunotherapies, has provided new treatment options and improved survival in patients with advanced stage hepatocellular carcinoma. Real‐world longitudinal observational studies can help understand the long‐term safety and effectiveness of these agents.