Abstract: Persistent hepatocellular secretory failure (PHSF) was def ined as acute liver injury induced by factors including drugs, toxicants, infections and transient biliary obstruction, where long-term severe hepatocellular cholestasis persisted even after the elimination of the inducing factors. PHSF was rare and its pathogenesis remained unclear. Conventional treatments were inef fective, and it could threaten patients’ lives in severe cases. Previous studies demonstrated that Rifampicin had favorable therapeutic ef f icacy and high safety for PHSF. This paper reported the diagnosis and treatment of one case of PHSF associated with UGT1A1 gene mutation, with the expectation that the analysis of this case would improve clinicians’ awareness and understanding of PHSF.