AIM To study the anticarcinogenic effect and acute toxicity of liver targeting mitoxantrone nanospheres. METHODS The anticarcinogenic effect of mitoxantrone polybutylcyanoacrylate nanoparticles (DHAQ PBCA NP) was investigated by using heterotopic and orthotopic transplantation models of human hepatocellular carcinoma (HCC) in nude mice and was compared with mitoxantrone (DHAQ) and doxorubicin (ADR). The acute toxicity of DHAQ PBCA NP lyophilized injection in mice was also studied. RESULTS The tumor inhibition rates of ADR, DHAQ, DHAQ PBCA NP to orthotopically transplanted HCC were 60 07%, 67 49% and 99 44%, respectively, but regard to heterotopically transplanted HCC, these were 80 03%, 86 18% and 92 90%, which were concordant with the results acquired by mitosis counting and proliferating cell nuclear antigen (PCNA). After iv administration to mice with DHAQ PBCA NP, the LD 50 was 16 9*!mg/*!kg ± 3 9*!mg/*!kg , no obvious local irritation was observed and there was no significant damage to the structure of liver cells, and that of the heart, spleen and kidneys. CONCLUSION The effect of DHAQ PBCA NP was significantly higher than that of DHAQ and ADR in the anti orthotopically transplanted HCC and the acute toxicity was relatively low. The AIM To study the anticarcinogenic effect and acute toxicity of liver targeting mitoxantrone nanospheres. METHODS The anticarcinogenic effect of mitoxantrone polybutylcyanoacrylate nanoparticles (DHAQ PBCA NP) was investigated by using heterotopic and orthotopic transplantation models of human hepatocellular carcinoma (HCC) in nude mice and was was With mitoxantrone (DHAQ) and doxorubicin (ADR). The acute toxicity of DHAQ PBCA NP lyophilized injection in mice was also studied. RESULTS The tumor inhibition rates of ADR, DHAQ, DHAQ PBCA NP to orthotopically transplanted HCC were 60 07%, 67 49. % and 99 44%, respectively, but regard to heterotopically transplanted HCC, these were 80 03%, 86 18% and 92 90%, which were concordant with the results acquired by mitosis counting and proliferating cell nuclear antigen (PCNA). After iv Administration to mice with DHAQ PBCA NP, the LD 50 was 16 9*!mg/*!kg ± 3 9*!mg/*!kg , no obvious local irritation was observe d and there was no significant damage to the structure of liver cells, and that of the heart, spleen and kidneys. CONCLUSION The effect of DHAQ PBCA NP was significantly higher than that of DHAQ and ADR in the anti orthotopically transplanted HCC and the acute toxicity Was relatively low.