In view of the association of CXCR4 expression with HCC progression, we designed CXCR4-targeted NPs to co-deliver sorafenib and metapristone to CXCR4-expressing HCC, with the purpose of enhancing the synergistic anti-tumor efficacy and reducing the off-target toxicity. Here, CXCR4 is linked to hepatocellular carcinoma.