Aerobic glycolysis, also known as the Warburg effect, is a hallmark of cancer and essential for metabolism in malignancies, but its regulation and modulation in cancer cells remain poorly understood. Here, using large-scale functional screening, we identified a tumor-associated and broadly expressed oncogenic long noncoding RNA LINC00973. Notably, knocking down LINC00973 significantly inhibits the proliferation of multiple types of cancer cells and reduces tumor growth in vivo. Mechanistically, LINC00973 directly binds to lactate dehydrogenase A (LDHA), an essential glycolytic enzyme, and enhances its enzymatic activity, thereby promoting glycolysis. Clinically, high expression of LINC00973 is significantly associated with poor prognosis in many types of human cancers. This work demonstrates that LINC00973 modulates cancer-specific regulation of the Warburg effect, and may represent a potential target for broad-acting anti-cancer therapies.Copyright © 2021 Science China Press. Published by Elsevier B.V. All rights reserved.