The currently recommended treatment for patients infected with hepatitis C virus (HCV) is pegilated interferon alpha (IFN alpha) plus ribavirin. Despite the numerous benefits of this therapy, there is an increasing concern regarding his tolerance. Among the most common side effects, interferon may trigger the onset or exacerbation of autoimmune diseases. When chronic hepatitis C coexists with an autoimmune disorder, it is not clear whether using interferon is better than avoiding it. We evaluated the disease state of a 55-year old female affected by sistemic sclerosis (SSc), during and after therapy with IFNalpha pegilated plus ribavirin for chronic HCV infection. We were worried about the potential worsening of the autoimmune disease during the therapy, but we were confident that we would give our patient a short course of peginterferon and ribavirin. A mild, asymptomatic worsening of lung SSc was observed during IFN administration, without life threatening symptoms. After 24 months follow up we observed the maintenance of the virological response and a good control of the rheumatological disease. Thus, in liver disease at high risk of progression and concomitant SSc, the antiviral therapy with IFNalpha is a feasible approach.