HClnc1 interacted with pyruvate kinase M2 (PKM2) to prevent its degradation and thus facilitated aerobic glycolysis and PKM2-STAT3 signaling.<h4>Conclusions</h4>HClnc1 is involved in a novel epigenetic mechanism of HCC tumorigenesis and PKM2 regulation. This evidence concerns the gene PKM and hepatocellular carcinoma.