Abstract: Objective To investigate the antagonism of selenium on oxidative stress and DNA damage induced by fluoride in primary hepatocytes of rats. Methods Primary hepatocytes of rats were isolated by using a modified two-step in-situ non-circulating perfusion method followed by multiple filtration and low-speed centrifugation. The blank control group,fluoride poisoning groups（ 250,500,1 000,2 000 μmol / L for 24 hours） and selenium intervening groups（ 10 or 100 nmol / L for 4 hours） were established. The contents of intracellular reactive oxygen species（ ROS）,malondialdehyde（ MDA）,glutathione（ GSH）,and activities of superoxide dismutase（ SOD） were measured. Meanwhile,the single cell gel electrophoresis（ SCGE） and micronucleus test were adopted to detect DNA damage. Results Compared with the blank control group,at fluoride concentration of 2 000 μmol / L,the contents of ROS and MDA were increased to 16. 78 ± 8. 32 and 11. 54 ± 3. 83 nmol / ml·prot,whereas the activity of SOD and the content of GSH were decreased（ 19. 53 ± 5. 28 NU / mg·port,21. 73 ± 15. 32 μg / mg·prot）; the comet rate（ 46. 25 ± 10. 60%）,comet tail length（ 31. 74 ± 9. 25 μm）, tail moment（ 15. 57 ± 7. 60）,and micronucleus rate（ 42. 80 ± 24. 61‰） were also increased significantly（ P ＜ 0. 01 for all）. In comparison with the fluoride poisoning group（ 2 000 μmol / L）,the contents of ROS and MDA in the 10 nmol / L selenium intervening group were decreased to 12. 36 ± 5. 15 and 7. 33 ± 0. 41 nmol / mg·prot,and the activity of SOD and the content of GSH were increased to 23. 72 ± 7. 15 NU / mg·prot and 26. 36 ± 14. 24 μg / mg · prot). Moreover,the comet rate（ 39. 27 ± 15. 09%）,comet tail length（ 24. 06 ± 8. 77 μm）,tail moment（ 9. 64 ± 4. 80）,and micronucleus rate（ 31. 28 ± 2. 65‰） were signifiicantly increased（ P ＜ 0. 05 for all）. Conclusion Selenium at proper dosage could antagonize oxidative stress and DNA damage induced by fluoride in primary hepatocytes of rats.