In the present study, CSP I-plus modified recombinant human Endostatin (rES-CSP) gradually decreased as Endostar in the kidney, spleen tissue, blood, but increased significantly in the liver and hepatocellular carcinoma tissues, which demonstrated that CSP I-plus modified Endostar(rES-CSP) improved the accumulation in liver and HCC cells, and significantly enhanced the inhibitory effects on tumor growth in nude mice with subcutaneous and orthotopic xenograft models of hepatocellular carcinoma HepG2. Here, COL18A1 is linked to hepatocellular carcinoma.