In this study, we demonstrate a reciprocal relationship between HIF-1α and Pol ι, whereby the activation of HIF-1α enhances Pol ι transcription, and alterations in Pol ι expression affect the stability of HIF-1α protein and subsequent progression of ESCC through enhanced binding of HIF-1α with USP7. Here, HIF1A is linked to esophageal squamous cell carcinoma.