In this study, we identified the promoter region of lnc‐APUE, verified that HNF4α directly interacted with the lnc‐APUE promoter to repress its transcription, and demonstrated that HNF4α downregulation represented an important mechanism responsible for lnc‐APUE upregulation in HCC. This evidence concerns the gene HNF4A and hepatocellular carcinoma.