Fluorosis is a major public health problem in numerous areas around the world, including China. To alleviate this problem, selenium has been used. In this study, we aimed to investigate the influence of selenium on apoptosis in fluorosis-affected rat livers and determine the optimal selenium concentration in drinking water to fight fluorosis. The protein levels of Fas in NaF and NaF+Se (0.375 and 0.75 mg/L) groups as well as FasL in NaF, Se (0.75 and 1.5 mg/L), and NaF+Se (0.375 mg/L) groups were significantly increased compared with those in the control group. The mRNA levels of Fas in NaF and Se (1.5 mg/L) groups as well as FasL in NaF and NaF+Se (0.375 mg/L) groups were significantly increased. The protein levels of Fas in NaF+Se (1.5 mg/L) group and FasL in three NaF+Se groups were significantly decreased compared with those in the NaF group. The mRNA levels of Fas in the three NaF+Se groups and FasL in NaF+Se (0.75 and 1.5 mg/L) groups were significantly decreased. Compared with the control group, activity of GSH-Px, and SOD in the NaF group decreased obviously and MDA content increased obviously; activity of SOD in 1.5 mg/L Se group decreased obviously. Compared with the NaF group, activity of GSH-Px in NaF+Se (1.5 mg/L) group significantly increased, and MDA content decreased obviously. Thus, fluoride induced apoptosis in the liver, thereby causing liver damage in the rats. Selenium could alleviate fluorosis-induced liver injury. In particular, selenium at 1.5 mg/L is considered the optimum concentration against fluorosis.