In this study the newly developed nilotinib derivative, SCT‐1015, suppressed the flux of aerobic glycolysis through inhibiting hexokinase 2, adjusting the metabolic direction to enhance the OXPHOS status by prohibiting pyruvate dehydrogenase kinase 1, and subsequently retarding HCC growth in vitro and in vivo (Fig. S12). The gene discussed is PDK1; the disease is hepatocellular carcinoma.