To investigate the effects of sodium fluoride (NaF) on apoptosis, c-Fos mRNA and protein expression levels, and methylation status as well as Dnmt1, Dnmt3a, and Dnmt3b mRNA expression levels in human embryo hepatocyte (L-02) which were exposed to different concentrations of NaF (0, 20, 40, and 80 mg/l) for 24 h in vitro. Results showed that the percentage of apoptosis and c-Fos mRNA and protein expression levels in 40 and 80 mg/l NaF-treated groups were higher than those in the control group (P<0.05). Further, Dnmt1 mRNA expression level was significantly decreased in the 80 mg/l NaF-treated groups compared to the control group (P<0.05); Dnmt3a and Dnmt3b mRNA expression levels were significantly decreased in 40 and 80 mg/l NaF-treated groups compared to the control group (P<0.05). c-Fos methylation levels, according to the bisulfite sequencing results, were decreased in 20, 40, and 80 mg/l NaF-treated groups against the control group. These results suggest that NaF could induce apoptosis and upregulate mRNA and protein expression level of c-Fos as well as decrease mRNA expression levels of Dnmt1, Dnmt3a, and Dnmt3b in L-02 cells. The decrease in c-Fos methylation levels might be involved in the early phase of apoptosis induced by NaF in L-02 cells.