Considering the limited reports on dual-targeted systems with both anti-CA IX antibody and BR2 in HCC treatment, we hypothesized that the surface modification of cantharidin-loaded liposomes with BR2 and CA IX antibody (DF-Lp), will improve the selectivity of the liposomes toward the over-expressed CA IX and help better cytosolic cantharidin delivery leading to enhanced anti-cancer effects, both, in vitro and in vivo. Here, CA9 is linked to hepatocellular carcinoma.