Objective To observe the effects of Siwu Tang formulation, which consists of fructose, ferulic acid, paeoniflorin, and ligustrazine hydrochloride (mass ratio of 9 008∶53∶721∶267), on the oxidative damage in irradiated AHH-1 cells, and to investigate the underlying protective mechanism. Methods AHH-1 cells were irradiated with a single dose of 4.0 Gy 60Co γ-rays, then cell viability, apoptosis and reactive oxygen species(ROS) level were measured. The activation of Nrf2-Keapl-ARE pathway was observed by transferring pGL4-ARE reporter gene transiently into HEK293 cells before the administration of Siwu Tang. Results At the concentration of 10 mg/L, Siwu Tang components formula had the best efficiency on anti-radiation damage. This drug inhibited the reduction of cell viability (t=-8.152, P<0.05), mitigated apoptosis (t=12.777, P<0.05), reduced intracellular ROS levels (t=3.465, P<0.05), and induced the expression of pGL4-ARE fluorescence reporter gene (t=-19.752, P<0.05). Conclusions Siwu Tang formulation has a protective effect against radiation by reducing radiation-induced oxidative damage through the activation of the Nrf2-Keap1-ARE signaling pathway. Key words: Siwu Tang formulation; Ionizing radiation; AHH-1 cells; Antioxidant; Nrf2-Keap1-ARE signaling pathway