Abstract: Objective To study the inhibiting effect of anti-OPN antibodies on tumor growth,metastasis,angiogenesis of HCCLM3 tumor in nude mice and its enhancement effect on radiotherapy. Methods HCCLM3 were inoculated subcutaneously into the right flank of 74 Balb/c nude mice.Next day after inoculation,50 mice were randomized into five groups（10 mice per group）：Group A (treatment with normal saline),Group B (treated with non-specific antibody),Group C,D,E (treated with 5 mg/kg,10 mg/kg,20 mg/kg of the anti-OPN antibodies,respectively).The treatments were repeated twice per week and tumor volume was measured every other day. At the end of the 10th week,nude mice killed,tumors and lungs of the mice were collected. Microvessel density (MVD) of tumor tissue was measured by IHC.The other 24 nude mice bearing HCC tumors were randomly divided into four groups：Group F (treated with normal Saline),Group G (treated with 6 MeV electron ray on the tumor),Group H (treated with 20 mg/kg anti-OPN antibody),Group I (treated with 20 mg/kg anti-OPN antibody and 6 MeV electron ray on the tumor).The tumor volume was measured every day and the enhancement factor (EF) was used to evaluate the radiation enhancement. Results Anti-OPN antibody had significant inhibiting effect on the tumor growth (P<0.01),as well as reduced metastasis (P<0.05) and angiogenesis (P<0.05) when comparing with control groups A,B. And among all of them, 20 mg/kg was the most remarkable dose. The inhibition rate of partial tumor growth in combination group I (41.67%),was higher than that of anti-OPN antibody group H （11.86%,P<0.01） and radiation group G(24.04%)（P<0.01). EF>1,which meant anti-OPN antibody had radiotherapy enhancement effect on implented tumor. ConclusionThe anti-OPN antibody can inhibit the tumor growth,metastasis,and angiogenesis and promote the radiotherapy enhancement of liver cancer,which would be another weapon for the HCC.