A study on mercury (Hg) and selenium (Se) concentrations in the liver and muscle of brown smooth-hound shark Mustelus henlei and its principal prey items, was conducted in the western coast of Baja California Sur, Mexico. Average Hg concentrations were found to be high in the muscle than in the liver; however, Hg concentrations were below the maximum permissible limits, and hence, the consumption of this species does not constitute a risk to human health. The mean Se concentrations were higher in the liver than in the muscle. The results of Hg: Se molar ratio revealed that Se counteracts the toxicity of Hg in hepatic tissues, whereas the contrary occurs in the muscle. Significant differences in Hg and Se accumulation were observed between females and males. Biomagnification factor values >1 demonstrate a biomagnification process from its principal prey species (i.e., red crab, Pleuroncodes planipes and Pacific mackerel, Scomber japonicus).