Background and aim Experts have reported thrombocytopenia is linked to chronic liver disease in up to 70% of patients with advanced fibrosis and portal hypertension. The occurrence of thrombotic thrombocytopenic purpura (TTP) with HCV infection is a rare and life-threatening event. We aim to investigate the causes of disturbed conscious levels, acute hemolytic anemia, and severe thrombocytopenia in a patient with chronic HCV and under treatment with direct-acting antivirals. Case report: Development of severe thrombocytopenia, acute hemolytic anemia, neurological symptoms in the form of fits and coma in a 32- year- older man with chronic HCV infection after one week of treatment with direct-acting antivirals (sofosbuvir 400mg PO daily, and daclatasvir 60 mg daily PO). Brain CT was normal, with a negative Coombs test and the presence of schistocytes in the peripheral blood smear. The patient presentation was suggestive of thrombotic thrombocytopenic purpura (TTP). Conclusion: This is a case of TTP after one week of direct-acting antiviral drugs despite the safety profile of these medications. Studying the pathophysiology of TTP after DAAs needs more clarification.