Contamination of shellfish products by different biotoxins is one of the most important issues leading to the concern of food safety, which directly related to the health of seafood consumers. Even miniscule doses of some algal toxins, such as domoic acid (DA) or saxitoxin, can cause severe illness or death in humans. Therefore, it's important to carry on the reseaches on biotoxins contamination in shellfish, especially in China, where the shellfish mariculture industry has become more and more important. Detection method targeted on domoci acid biotoxin has been developed using liquid chromatography in China but little information is available on its Confirming Method. In this study, a high-performance liquid chromatography-tandem mass spectrometric method was established for the determination of residue of domoic acid in shellfish. Shellfish samples were collected from Zhejiang Province from March to Novermber in 2007. DA were extracted from homogenized samples with 50% methanol solution, followed by clean-up of the extracts with LC-MAX column, and eluted by citrate solution. Two daughter ions (m/z 803.5/255.1, m/z 803.5/563.1) were scanned, analyte identification were performed by electrospray ionization (ESI) in positive mode using MRM and the quantification were performed using external standard method. The conditons of high-performance liquid chromatography-tandem mass spectrometry were as follows, positive ion electrospray ionization (+ESI) mode, IS + 5250V, TEM 475℃, DP100V, FP325V, NEB8, CUR11, EP8, CAD10, CXP17, CE23(m/z312.1/266.4), CE34(m/z312.1/162.4). The mobile phase of HPLC was the acetonitrile; 0.1% acetic acid water solution (vol/vol:20:80) and the chromatographic column was Zorbax XDB-C₁₈ (2.1 mm×150 mm×5 μm). The result showed that the limit of detection was 0.02 μm·g^-1, and the linear range was 0.02 μm·g^-1-8.0 μm·g^-1. At spiked level of 0.02 μm·g^-1-4.00 μm·g^-1, the average recoveries of DA were 80.2%-92.2%, RSD were 4.42%-9.46%, respectively. A batch of main aquacultre shellfishes collocted along the Zhejing coast was evaluated using the above method. The results showed that the LCMSMS method is sensitive, reliable, selective and specific for the determination of domoic acid.