Pulmonary arterial hypertension (PAH) is known to develop as a consequence of multiple genetic and/or non-genetic factors. A 27-year-old woman with chronic hepatitis C virus (HCV) infection developed severe PAH after interferon (IFN) therapy. Although most of the reported clinical courses of IFN-induced PAH are poor despite the discontinuation of IFN, the present patient was successfully treated with a triple combination therapy. In this report, we discuss the crosstalk among chronic HCV infection, IFN therapy, autoimmune disorders, and portal hypertension in the pathogenesis and development of PAH.