OBJECTIVES: Excessive fluoride ingestion causes a disease known as Fluorosis. Selenium supplementation could antagonize the bovine fluorosis. So we want to investigate how the dietary selenium supplementation to influence the gene expression of p38, p65, and caspase-3 in fluorosis patients. METHODS: Ziyang County of Ankang City has higher environmental selenium level, while fluorosis patients who lived in have the habit of tea drinking, especially in Haoping Town. Hanbin district of Ankang City has lower environmental selenium level was choose as selenium internal control. The fluorosis patients from different environmental selenium level area and the healthy volunteer were divided into three groups: “High Se + F group” (n=20), “High F group” (n=20) and “Control group” (n=20). p38, NF-kB p65 and caspase-3 mRNA level were examined by RT-PCR. β-actin served as determining control The concentration of fluoride in serum and urine, the content of Se in hair were also determined. RESULTS: The concentration of fluorine in “High F group” and “High Se + F group” in serum and urine was higher than that in “Control group” (urine 3.2731±0.26, 3.2744±0.31 and 0.7923±0.14, respectively; serum: 0.3996±0.03, 0.3888±0.09, 0.0922±0.01, respectively). The mean for total Se concentration in hair was different: 2.5005±0.27 in “High Se + F group”, 0.6075±0.07 in “High F group” and 0.5215±0.05 in “Control group”, respectively. The mRNA level of p38, NF-kB p65 and caspase-3 was significantly high in “High F group” than that in “High Se + F group” and “Control group” (p38:5.0009±0.65, 1.2749±0.09, 1.0574±0.13, respectively; NF-kB p65: 3.5248±0.47, 1.9845±0.14, 1.9976±0.15, respectively; caspase-3:2.2936±0.23, 1.2841±0.19, 1.3590±0.18, respectively). CONCLUSIONS: These results suggest that dietary high selenium intake help people who suffering fluorosis lessen damage by reduce the gene expression of p38, then reduce NF-kB p65 gene expression and at last lower the gene expression of caspase-3.