Overall, through in vitro and in vivo experiments, the current work revealed that DT‐13, a steroidal saponin derived from the tuber of Liriope muscari (Decne) Baily, inhibits the aerobic glycolysis, proliferation, and survival of HCC cells via the c‐myc/PFKL signaling axis. The gene discussed is PFKL; the disease is hepatocellular carcinoma.