We report a rare case of marked elevation of α-fetoprotein in the absence of hepatocellular carcinoma caused by a relapse of hepatitis C virus (HCV) infection. A 58-year-old man underwent liver transplantation to treat hepatocellular carcinoma caused by HCV-related liver cirrhosis. The HCV was of genotype 2a, and the ribonucleic acid titer was >8.0 log IU/mL. Direct-acting antiviral drugs were prescribed for 12 weeks; however, the HCV infection relapsed after treatment had ended, and α-fetoprotein levels increased to 8,981 ng/mL. Imaging did not reveal any malignancies. The patient initiated interferon therapy, at which time AFP levels decreased, and the HCV was successfully cleared.