In this study, fluoride‐induced ROS were a harmful by‐product of mitochondrial respiration and activated caspase‐3 apoptosis pathway under stress conditions; it was proved that the protein levels of Bcl‐2 were down‐regulated, whereas caspase‐3, Bax and caspase‐9 were up‐regulated, in the fluorosis group, with cell death in this group significantly increased in in vivo and in vitro experiments. Here, BCL2 is linked to dental fluorosis.