Emerging evidence has uncovered the extremely important roles of long noncoding RNAs (lncRNAs) in the progression of malignant tumors which includes numerous processes of gene regulation. LncRNA NR2F1-AS1 has been confirmed to have close correlation with the tumorigenesis of diverse cancers. However, the underlying regulatory function of it on esophageal squamous cell carcinoma (ESCC) progression is poorly known and thus needs more elucidations. In this study, a markedly elevated expression of NR2F1-AS1 was discovered in ESCC cells. Functional assays demonstrated that NR2F1-AS1 deficiency repressed ESCC progression. Molecular mechanism tests verified that knockdown of NR2F1-AS1 could lower the expression of GLI2 (a key protein molecule of Hedgehog signaling pathway) in ESCC. Additionally, NR2F1-AS1 was confirmed to facilitate ESCC progression via activation of Hedgehog signaling pathway. NR2F1-AS1 activated Hedgehog signaling pathway by regulating GLI2 to upregulate NR2F1 expression in ESCC. Besides, NR2F1 was testified to activate NR2F1-AS1 transcription in ESCC. Final rescue assays further demonstrated that NR2F1 upregulation could reverse the NR2F1-AS1 knockdown-mediated function on ESCC progression. Briefly, NR2F1-induced NR2F1-AS1 promotes ESCC progression through activation of Hedgehog signaling pathway. (C) 2019 Elsevier Inc. All rights reserved.