In this study, we not only clarified the mechanism by which HNK inhibits the glycolysis of cancer cells but also identified E3 ubiquitin ligase in the ubiquitination process of HIF-1α; however, the mechanism through which HNK promotes the ubiquitination degradation of HIF-1α via UFL1 and BRE1B remains to be further studied—this will help better understand the role of HNK in the energy metabolism of tumor cells. This evidence concerns the gene RNF40 and cancer.