A significant proportion of HIV patients, ranging between 5-67%, are co-infected with hepatitis B virus (HBV). Several studies suggest an increasing incidence of hepatocellular carcinoma (HCC) in HIV infected individuals. We report the case of a 69 years old male co infected with HBV and HIV who developed HCC. The patient was unfit for curative approach and he underwent three sessions of transcatheter arterial chemoembolisation (TACE). After the last session the disease assessment showed progression and sorafenib therapy was initiated. Highly active antiretroviral therapy (HAART) was continued during sorafenib treatment. The patient achieved a radiological complete response (CR) after 6 months of therapy and remained with no sign of HCC progression at subsequent assessment. Meanwhile, patient's HIV and HBV infections remained stable. Regarding toxicity the patient developed grade 3 hand foot skin reaction (HFSR) that required 50% dose reduction of sorafenib, grade 3 hypertension and grade 2 diarrhea. In conclusion this is the first case of successful treatment of HCC in a HIV-HBV co-infected patient and only the second report of the co administration of sorafenib with HAART.