In this study, the SLC7A11 shRNA (shSLC7A11) gene delivery system G−LPQDEA/shSLC7A11 was developed using esterase-responsive polymers, PQDEA, and HCC-targeting long-circulating liposomes (galactose-decorated DSPE-PEG, cationic lipid DOTAP, and phospholipid DOPC). Here, SLC7A11 is linked to hepatocellular carcinoma.