Severe cholestatic hepatitis C (SCH) is a unique variant of recurrent hepatitis C that occurs after liver transplantation. Unfortunately, the prognosis of SCH is poor, and interferon (IFN) therapy has been reported to not improve the prognosis. We herein report a case of progressive SCH with acute cellular rejection (ACR) and bacterial infection, which was successfully treated using IFN-free therapy with daclatasvir and asunaprevir. A 43-year-old man was diagnosed with SCH and mild ACR at day 48 after liver transplantation, and IFN-free therapy with daclatasvir and asunaprevir was started. Although he experienced catheter-related bacteremia on the first day, the IFN-free therapy was safely continued, which immediately caused his liver function to improve. His bilirubin levels decreased from 11.1 to 2.1 mg/dL and serum hepatitis C virus RNA levels became undetectable after 4 weeks of the treatment. This case indicates that IFN-free therapy for progressive SCH with acute cellular rejection and bacterial infection is safe and effective, and may improve the outcomes of hepatitis C virus positive transplant recipients.