Worldwide, chronic hepatitis B virus infection remains the main aetiology of hepatocellular carcinoma, while human immunodeficiency virus may hasten the evolution of hepatocellular carcinoma in those co-infected with hepatitis B virus/human immunodeficiency virus. We describe a 29-year-old female with unmonitored hepatitis B virus infection for over 5 years, human immunodeficiency virus disease on a tenofovir-based antiretroviral regimen for 11 months, who presented with a 2-week history of epistaxis and abnormal vaginal bleeding, associated with unintentional weight loss of 4 months duration. After extensive investigation, a definitive diagnosis of hepatocellular carcinoma was established based on histopathological assessment in the presence of a positive hepatitis B envelope antigen, mildly raised alpha feto-protein, and a non-cirrhotic liver. Periodic surveillance for hepatocellular carcinoma in patients with chronic hepatitis B virus infection is important, particularly in those with evidence of actively replicating hepatitis B virus for early detection and implementation of curative therapies to reduce mortality and morbidity.