The article presents a hepatocellular carcinoma cell surface-specific ligand glycyrrhetinic acid (GA) and cell-penetrating peptide (TAT) with good cell membrane penetration to modify the anti-tumor drug pingyangmycin (PYM) liver delivery system, which achieve targeted delivery of drugs and improve anti-tumor efficiency. In this study, we synthesized the pingyangmycin liposome modified by glycyrrhetinic acid and cell penetrating peptide(GA-TAT-PYM-L) and evaluated the anti-tumor effect of GA-TAT-PYM-L in vitro . Using the 3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenylte-trazolium bromidecell proliferation method, GA-TAT-PYM-L had a stronger inhibitory effect on HepG2 cells than the free drug PYM at the same concentration. Acridine orange-ethidium bromide staining assays showed that GA-TAT-PYM-L had stronger apoptosis promotion effects on HepG2 cells in comparison to PYM. Pharmacokinetic studies indicated that, compared with PYM, GA-TAT-PYM-L enhanced mean residence time (MRT 0-∞ ) and area under curve (AUC 0-∞ ) by about 2.79-fold and 2.45-fold. The T 1/2 was prolonged to 140.23 ± 14.13 min. Tissue distribution results showed that the PYM concentrations in livers from the GA-TAT-PYM-L group were always higher than other tissues at each monitoring period after 5 min, indicating that GA-TAT-PYM-L can achieve liver targeting.