As top predators in the Pearl River Estuary (PRE) of China, Indo-Pacific humpback dolphins (Sousa chinensis) are bioindicators for examining regional trends of environmental contaminants in the PRE. We examined samples from stranded S. chinensis in the PRE, collected since 2004, to study the distribution and fate of total mercury (THg), methylmercury (MeHg) and selenium (Se) in the major tissues, in individuals at different ages and their prey fishes from the PRE. This study also investigated the potential protective effects of Se against the toxicities of accumulated THg. Dolphin livers contained the highest concentrations of THg (32.34±58.98 µg g−1 dw) and Se (15.16±3.66 µg g−1 dw), which were significantly different from those found in kidneys and muscles, whereas the highest residue of MeHg (1.02±1.11 µg g−1 dw) was found in dolphin muscles. Concentrations of both THg and MeHg in the liver, kidney and muscle of dolphins showed a significantly positive correlation with age. The biomagnification factors (BMFs) of inorganic mercury (Hginorg) in dolphin livers (350×) and MeHg in muscles (18.7×) through the prey fishes were the highest among all three dolphin tissues, whereas the BMFs of Se were much lower in all dolphin tissues. The lower proportion of MeHg in THg and higher Se/THg ratios in tissues were demonstrated. Our studies suggested that S. chinensis might have the potential to detoxify Hg via the demethylation of MeHg and the formation of tiemannite (HgSe) in the liver and kidney. The lower threshold of hepatic THg concentrations for the equimolar accumulation of Se and Hg in S. chinensis suggests that this species has a greater sensitivity to THg concentrations than is found in striped dolphins and Dall’s porpoises.