〔Abstract〕 Objective To explore the mechanism of nuclear factor E2-related factor 2(Nrf2) in bleomycin(BLM)-induced DNA damage of lung cancer cells. Methods The fluorescence intensity of tissue reactive oxygen species(ROS) in human lung cancer cells A549 and H1299 was detected by a reactive oxygen species fluorescent probe(DCFH-DA). DNA damage of A549 and H1299 cells treated with 5 μg/ml BLM was detected by Western blot and micronucleus. Then, the Nrf2-low expression transient siRNA and the stably shRNA-transformed lung cancer cells were respectively constructed to detect the DNA damage after BLM. The interaction between Nrf2 and Rad51 in cells was detected by co-immunoprecipitation method. Results Under the action of BLM, ROS levels in A549 and H1299 cells increased significantly, and Nrf2 entered the cell nucleus for activation(P<0.01). Under the effect of BLM, resveratrol(Res) stimulated A549 and H1299 cells to up-regulate the protein expression of Nrf2(P<0.01), while the expression of DNA damage marker protein γ-H2 AX decreased(P<0.01). On the contrary, after interfering the protein expression of Nrf2 in A549 and H1299 cells with siRNA, the protein expression of γ-H2 AX in A549 and H1299 cells was significantly up-regulated under the action of BLM(P<0.01). Western blot results showed that the expression of homologous recombination repair protein Rad51 and the expression of Nrf2 protein in A549 cells with low Nrf2 expression were significantly down-regulated(P<0.01). Conclusion The antioxidant transcription factor Nrf2 in tumor cells can interact with Rad51 to regulate the expression of Rad51 and reduce BLM-induced cellular DNA damage.