OBJECTIVE: To investigate the toxic effect of sodium fluoride (NaF) on the nematode Caenorhabditis elegans (C. elegans). METHODS: Adult C. elegans were exposed to different concentrations of NaF (0.038 mmol/L, 0.38 mmol/L, and 3.8 mmol/L) for 24 h. To assess the physiological effects of NaF, the brood size, life span, head thrashes, and body bend frequency were examined. Reactive oxygen species (ROS) and cell apoptosis were detected as parameters of biochemical response. The gene expressions were determined by real-time polymerase chain reaction (PCR) to assess the molecular-level response. RESULTS: At the physiological level, the brood size of C. elegans exposed to 0.038 mmol/L, 0.38 mmol/L, and 3.8 mmol/L concentrations of NaF were reduced by 6%, 26%, and 28% respectively in comparison with the control group. The maximum life spans of C. elegans exposed to 0.038 mmol/L, 0.38 mmol/L, and 3.8 mmol/L concentrations of NaF were reduced by 3 days and 5 days, respectively. Head thrashes and body bend frequency both decreased with increasing concentrations of NaF. At the biochemical level, the production of ROS and the incidence of cell apoptosis increased with increasing concentrations of NaF (P < 0.05). At the molecular level, different concentrations of NaF exposure raised the expression of stress-related genes, such as hsp16.1, sod-3, ctl-2, dhs-28, gst-1, and cep-1. CONCLUSION: NaF exposure could induce multiple biological toxicities to C. elegans in a concentration-dependent manner. These toxicities may be relevant to the oxidative stress induced by increased ROS production and accumulation in C. elegans.