Aquatic products are an important source of environmental pollutants to humans. This study was conducted to assess the bioaccessibility of selected brominated flame retardants and heavy metals in common aquatic products from the Pearl River Delta, South China, as well as associated human health risks. Based on a questionnaire survey, ten of the most consumed aquatic products were collected from local markets. The bioaccessibility of polybrominated diphenyl ethers (PBDEs), hexabromocyclododecane (HBCDDs), and heavy metals was assessed using an in vitro gastrointestinal model. Bioaccessibility of heavy metals (33.0%–84.0%) and HBCDDs (38.5%–68.4%) was significantly higher than that of PBDEs (13.4%–65.4%). Total non-carcinogenic and carcinogenic risks from heavy metal consumption were much higher than the threshold values due to excessive abundances of arsenic in shellfish (HQ=2.45, CR=1.1×10^-3). Furthermore, middle-aged populations and females were subjected to greater health risks due to different intakes of aquatic products among age and gender groups. Significant difference in bioaccessibility among analytes indicated that bioaccessibility of pollutants is non-negligible in health risk assessment. This is the first study systematically investigating health risks of aquatic products consumption and concludes that shellfish is a great cause for concern for the PRD residents.