Objective To prepare the quality control materials (QCMs) of mercury, arsenic in marine fish and implement the proficiency test in the centers for disease control and prevention that are responsible for national food safety risk monitoring. Methods Sixteen species of marine fish were collected from Guangdong Province and the total mercury and arsenic in these samples were determined using direct mercury analyzer (DMA) and inductively coupled plasma mass spectrometry (ICP-MS) respectively. Epinephelus lanceolatus was selected to prepare the QCMs, which was cultivated in deep sea cages. The procedure of preparing QCMs included freeze mincing the muscle, drying, degreasing, comminution and seal package. One way ANOVA was used for evaluating the homogeneity of QCMs, and t test for the stability. ResultsThe experimental result showed that the Epinephelus oanceolutus QCMs remained well homogeneous and stable. The QCMs were used for proficiency testing which 193 laboratories had taken part in, the satisfactory performance rates of total mercury and arsenic were 81.1% and 80.2% respectively. DMA for mercury determination and ICP-MS for arsenic determination were the most efficient method. Conclusion The fish powder QCMs were suitable for total mercury, arsenic in food proficiency testing. This research provide method ology reference for both preparation of seafood based QCMs and edition of national food safety standard.