BACKGROUND: Long-term excessive intake of fluoride, especially through drinking water, can cause chronic fluorosis of bone. The disease can lead to bone damage and deformity, and is difficult to recover.Unfortunately, we have not developed a noninvasive or minimally invasive method for its early diagnosis. OBJECTIVE: To observe the expression of apoptosis-related miRNAs under the action of excessive fluorine in human osteoblasts. METHODS: The fluorine model was established in the human osteoblasts by cultured with 20 and 40 mg/L sodium fluoride for 24 and 48 hours, respectively. The expression levels of apoptosis-related miRNAs were determined by PCR array. RESULTS AND CONCLUSION: After 24-hour treatment of sodium fluoride, 48 kinds of miRNAs were upregulated and 4 ones were down-regulated in the osteoblasts. After 48-hour treatment of sodium fluoride, 21 kinds of miRNAs were upregulated and 2 ones were down-regulated. It showed that nine up-regulated miRNAs and one down-regulated miRNA were same in two periods. The 10 miRNAs are selected for target gene analysis on bioinformatics software that refer to the effect of anti-apoptosis and pro-apoptosis, which is of great significance for the early identification of skeletal fluorosis.