In order to gain insights into the chronic effects and mechanisms of hexabromocyclododecane (HBCD), the animal model Caenorhabditis elegans (C.elegans) was chosen for toxicity study. Multiple endpoints, including the physiological (growth and locomotion behaviors), biochemical (reactive oxygen species (ROS) production, lipofuscin accumulation, and cell apoptosis), and molecular (stress-related gene expressions) levels, were tested by chronic exposure for 10d to low concentrations of HBCD (0.2nM-200nM). The results revealed that chronic exposure to HBCD at concentrations more than 20nM would significantly influence the growth, locomotion behaviors, ROS formation, lipofuscin accumulation, and cell apoptosis of nematodes. Treatment with antioxidants of ascorbate and N-acetyl-l-cysteine (NAC) suppressed the toxicity induced by HBCD. The integrated gene expression profiles showed that the chronic exposure to 200nM of HBCD significantly increased the expression levels of stress-related genes (e.g.,
hsp-16.2,
hsp-16.48,
sod-1,
sod-3, and
cep-1 genes). Among these genes, the
sod-1,
sod-3, and
cep-1 gene expressions were significantly correlated with HBCD-induced physiological effects by the Pearson correlation test. The mutations of
sod-3 and
cep-1 induced more severe toxicity compared to wild-type nematodes. Therefore, HBCD exposure induced oxidative stress by ROS accumulation and cell apoptosis, which resulted in HBCD-induced toxicity on nematodes, and
sod-3 and
cep-1 played important roles in protecting nematodes against HBCD-induced toxicity.