Hepatitis B virus and hepatitis C virus are the two most common causes of chronic liver disease in the world. Dual infection with hepatitis B virus and hepatitis C virus, whose prevalence is underestimated, is characterized by a more severe liver injury, a higher probability of liver cirrhosis and a higher incidence of hepatocellular carcinoma. Treatment of these patients represents a therapeutic challenge. We report the case of an hepatitis B virus-hepatitis C virus co-infected patient, which particularly illustrates the interactions between these two viruses and therapeutic problems caused by the dual infection. HCV was initially dominant, which indicated a combination therapy by pegylated interferon and ribavirin. This treatment was associated with an early virological response of the HCV but an increase of HBV DNA occurred, requiring the use of a nucleoside analogue. A good response was obtained for the HBV but a relapse of HCV was noted, posing a problem for therapeutic decision.