Introduction: Hepatocellular carcinoma (HCC) ranks the fifth most common cancer among men and the seventh among women globally. It is aggressive with hepatitis fibrosis or cirrhosis being the most common end-stage. The well know risk factors includes chronic infection with Hepatitis B virus (HBV) and hepatitis C virus (HCV) while habitual betal gum chewing and secretan have been implicated. The most effective measure to prevent or reduce the incidence of HCC is by utilizing antiviral agents. This study is to review combined antiretroviral therapy (cART) in HBV & HCV-associated confirmed HCC. Methods: A systematic review of randomized controlled trials published in Pub Med and Clinical Trials Sites will be carried out. Citation of included studies will be checked to identify additional studies not identified in the electronic searches. It will include any randomized controlled studies that considered combined ART in HBV & HCV associated HCC. Data extraction and analysis will be performed. The extracted data will be discussed, decision documented and, where necessary the authors of the studies will be contacted for clarification. Ethics & Dissemination: Ethical approval is not required given that this is a protocol for a systematic review. The finding of this study will be presented at the 12th Clinical Microbiology Conference in Spain and also published in peer reviewed journal. Updates of the review will be conducted every two years to inform and guide healthcare practice.