Mechanistic studies revealed that TZP suppressed the expression of key glycolytic enzymes, PFK‐1 and PFKFB3, by promoting the ubiquitination and degradation of HIF‐1α, significantly inhibiting the tumor tissues' glycolytic metabolic flux (evidenced by reduced ECAR and decreased pyruvate/lactate production), while also lowering the expression of glucose transporters (GLUT1/4/12) and the levels of TCA cycle intermediates. Here, PFKFB3 is linked to neoplasm.