Our present results indicate that ESRRG functions as a negative transcriptional regulator of the glycolysis pathway, and overexpression of ESRRG in ESCC cells significantly inhibits the transcriptional translation of several key enzymes in the glycolysis pathway, such as hexokinase 2 (HK2), aldolase A (ALDOA), enolase 1 (ENO1), pyruvate kinase M2 (PKM2), and lactate dehydrogenase A (LDHA). Here, HK2 is linked to esophageal squamous cell carcinoma.