Esophageal cancer is one of the most common malignant cancers worldwide. Long non-coding RNAs (lncRNAs) have been reported to be associated with different types of cancer; however, the precise function of lncRNAs in tumorigenesis remains largely unknown. Herein, we found that lncRNA NBAT-1 levels were lower in EC clinic tissues than in normal samples, and lncRNA NBAT-1 expression was negatively associated with prognosis and TNM stage in EC patients. More importantly, in EC cancer cells, lncRNA NBAT-1 overexpression strongly inhibited cell proliferation, cell growth and tumor glycolysis. Furthermore, a series of rescue experiments were performed to demonstrate that the role of lncRNA NBAT-1 in EC cell proliferation, cell growth and tumor glycolysis was partially dependent on the PKM2 protein, which is a key metabolic enzyme in tumor development. Taken together, our data illustrate a functional role for lncRNA NBAT-1 in metabolic reprogramming in EC cancer; thus, lncRNA NBAT-1 might be a potential clinical therapeutic target in EC patients.