We demonstrate that MZF1 is up-regulated in NB tissues and cells, and facilitates the aerobic glycolysis, growth, and aggressiveness of NB cells by up-regulating HK2 and PGK1. Meanwhile, MZF1-uPEP interacts with Yin Yang 1 (YY1) to repress its transactivation, resulting in transcriptional inhibition of MZF1 and downstream glycolytic genes. The gene discussed is HK2; the disease is neuroblastoma.