The radioprotective effects and molecular mechanisms of black tomato powder (BTP) in mice were investigated in this study. ICR mice irradiated by 5Gy ⁶⁰Coγ were treated with BTP (1.5,3.0, and 4.5g/kg body weight). After 14 days' treatment, thymus and spleen indices, white blood cells' number (WBC), bone marrow cells' number, spleen lymphocytes, cytokine levels, NF-κB, and I-κB were investigated. The results revealed that the thymus index was significantly(P<0.05)higher in mice treated by 4.5g/kg BTP while mice in the 3.0 g/kg BTP treatment group had the significantly(P<0.05)higher bone marrow cells' number compared with the irradiation (IR) control group. Compared with the IR control group, the spleen lymphocytes in the 1.5g/kg BTP treatment group were significantly(P<0.01)different. The 4.5g/kg BTP treatment also inhibited the increasing of IL-1α和IL-10. Moreover, the 3.0g/kg and 4.5g/kg BTP treatment decreased the hepatic MDA contents and increased the hepatic GSH-Px and SOD contents. Meanwhile, the 4.5g/kg BTP treatment could also increase the serum SOD content. The radioprotective effects of BTP might be due to the modulation of the expression of NF-κB and I-κB, which could further modulate the proinflammatory cytokines release and immune responses.