In this study, we highlighted the roles of TMEM161B‐AS1 in ESCC development, progression and prognosis and demonstrated that TMEM161B‐AS1 blocked cell proliferation, invasion and glycolysis of ESCC cells by absorbing miR‐23a‐3p to enhance HIF1AN expression, further eliciting the inhibition of glycolysis‐related proteins. Here, TMEM161B is linked to esophageal squamous cell carcinoma.