This paper reports the result of an experiment on the anticarcinogenic effect of liver targeted drug delivery system-mitoxantrone-polybutylcyanoacrylate-nanospheres (DHAQ-PBCA-NS) by using a model of heterotopic and orthotopic transplantation of human hepatocellular carcinoma (HCC) in nude mice. No significant difference was noted between the anti-HCC effects of mitoxantrone and dexerubicin, but the anti-orthotopic transplanting HCC effect of mitoxantrone-nanospheres was obviously higher than that of mitoxantrone and dexerubicin by comparison of tumor inhibition rates and proliferating cell nuclear antigen (PCNA). The result showed the applicability of mitoxantrone-nanospheres.