Thrombocytopenia is a major problem for the patients with chronic hepatitis C. It has a multifactorial pathophysiology with many different mecanisms. Its presence may be a limiting factor when considering antiviral therapy and may be associated with decreased sustained virological response rates. Thrombocytopenia can increase the risk of bleeding and may impede the initiation of different invasive diagnostic and therapeutic procedures. Eradication of HCV infection is the most practical strategy for the remission of thrombocytopenia. The recent change in DAAs without IFN, as the frontline therapy for HCV, permit to avoid the dilemmas associated with initiating or maintaining IFN based antiviral therapy.