Objective To study the expression of apoptosis-associated genes and the role of apoptosis in acute radiation-induced liver injury. Methods A mouse radiation model, which was irradiated with ⁶⁰Co γ ray, was established in this study, and the pathological changes were observed by light and electron microscopy for 48 hours. Western blotting analysis was used to measure the expression of some proteins (Caspase 3,Caspase 8, Bcl-2, Bcl-x_L, Bax, Bad, PUMA, Slug) and TUNEL assay was employed to examine cell apoptosis in mouse liver. Results Degeneration and apoptosis were found in the liver at 4 h after irradiation and necrosis occurred at 12 h after irradiation. The peak of apoptosis with activation of Caspase 3 in liver was detected during 24-48 h after irradiation. Bcl-2 protein expression was up-regulated during 4-24 h after irradiation, then was down-regulated at 48 h; PUMA protein was up-regulated during 4-48 h after irradiation; Bcl-x_L and Bad protein were up-regulated during 6-48 h after irradiation; and Bax and Slug protein were up-regulated only at 12 h after irradiation. Conclusion Up-regulation of BH3-only members (PUMA and Bad) after irradiation may be associated with the increase of apoptotic cells in the liver.