Objective: To evaluate the safety and efficacy of metformin in patients with type 2 diabetes mellitus (T2DM) and chronic hepatitis C virus (HCV) with or without cirrhosis and hepatocellular carcinoma (HCC). Data Sources: A PubMed (1946-August 2013) search using the keywords type 2 diabetes mellitus, metformin, hepatitis C virus, cirrhosis, and hepatocellular carcinoma was conducted. The references in published articles were reviewed to identify additional references for inclusion. Study Selection and Data Extraction: Studies written in English, evaluating metformin use in human patients with T2DM and chronic HCV were included. Data Synthesis: Eight studies met criteria for inclusion. Two prospective, randomized controlled trials showed increased benefit with metformin on virological response in patients with insulin resistance receiving HCV treatment. A prospective observational study evaluated metformin exclusively in patients with T2DM and HCV and showed significant reductions in the occurrence of HCC, liver-related death, and liver transplant. Four retrospective case control studies showed a decreased risk of HCC with metformin treatment in patients with T2DM and chronic liver disease. Finally, a retrospective cohort study indicated an increased survival rate in patients with diabetes and HCC undergoing radiofrequency ablation. Although diarrhea was increased in patients receiving metformin, no serious adverse effects, including lactic acidosis, were reported. Conclusions: Metformin may provide benefit in the treatment of HCV and in reducing the risk of HCC in patients with T2DM and HCV. Further long-term, randomized controlled trials are needed to adequately assess the safety and efficacy of metformin therapy in patients with comorbid diabetes and chronic HCV.