This case report aims to explore the efficacy and safety of upadacitinib in patients with severe atopic dermatitis during hepatitis C activity period, providing reference for the treatment of severe atopic dermatitis patients in clinical hepatitis C activity period. We reviewed the treatment history of a patient with severe atopic dermatitis with hepatitis C in our hospital and analysed the safety of applying upadacitinib for the treatment of severe atopic dermatitis in conjunction with the review of relevant literature. During the 1-year follow-up, the patient's peripheral rash gradually improved, and the hepatitis C viral RNA load was normalised at the 6-month follow-up, reaching the clinical criteria for hepatitis C cure. The patient took only oral triamcinolone and upadacitinib for half a year after hepatitis C cure, and no recurrence of hepatitis C or liver function abnormality was found. Upadacitinib can be considered as a treatment option for patients with severe atopic dermatitis during hepatitis C activity period, but more clinical cases and drug research are needed to assess its safety during hepatitis C activity period.