Metabolism reprogramming is one of the hallmarks of cancer cells, especially glucose metabolism, to promote their proliferation, metastasis and drug resistance. Cancer cells tend to depend on glycolysis for glucose utilization rather than oxidative phosphorylation, which is called the Warburg effect. Genome instability of oncogenes and tumor-inhibiting factors is the culprits for this anomalous glycolytic fueling, which results in dysregulating metabolism-related enzymes and metabolic signaling pathways. It has been extensively demonstrated that protein-coding genes are involved in this process; therefore, glycolysis-targeted therapy has been widely used in anti-tumor combined therapy via small molecular inhibitors of key enzymes and regulatory molecular. The long non-coding RNA, which is a large class of regulatory RNA with longer than 200 nucleotides, is the novel and significant regulator of various biological processes, including metabolic reprogramming. RNA interference and synthetic antisense oligonucleotide for RNA reduction have developed rapidly these years, which presents potent anti-tumor effects both in vitro and in vivo. However, lncRNA-based glycolysis-targeted cancer therapy, as the highly specific and less toxic approach, is still under the preclinical phase. In this review, we highlight the role of lncRNA in glucose metabolism and dissect the feasibility and limitations of this clinical development, which may provide potential targets for cancer therapy.