Esophageal cancer (EC) is the 2nd fatal gastrointestinal tract malignancy and the sixth most predominant driver of cancer-associated mortality worldwide. Interestingly, long non-coding RNAs (lncRNAs) have a sequence of more than 200 base pairs and are regarded as one of the epigenetic elements. LncRNAs have been demonstrated to influence EC features comprising initiation, development, angiogenesis, invasion, and metastasis. Notably, lncRNAs could modulate the expression of several genes and chromatin architectures which are implicated in EC pathogenesis. Besides, numerous lncRNAs have a crucial role in the chemotherapeutic response of EC cells. Furthermore, lncRNAs are thought to be a promising biomarker in EC whose expression patterns can distinguish between EC subtypes and stages as well as predict cancer aggressiveness. Thus, the current review emphasizes the latest updates on the modulatory functions of lncRNAs in EC pathogenesis, their significance to the EC cells' therapeutic response, and their clinical efficacy as prognostic and diagnostic biomarkers.