A method of the high performance liquid chromatography-tandem mass spectrometry was established to detect acids shellfish poisoning (domoic acid) residues in aquatic products. Toxin was extracted with 50% methanol by ultrasonic. The supernatant was purified by solid phase extraction column to purification after centrifugation, then was subjected to HPLC-MS/MS analysis. Under the optimized conditions of LC and MS, DA showed a good linear relationship when its concentrations were 20.0 to 1000.0 μg/ L (R2>0.999). Under the added concentrations between 20.0 and 100.0 μg/ kg level, the average recovery rates were 71.3% to 84.1%, and the coefficients of variation were 4.4% to 4.6%. The detection limit of DA was 5.0 μg/ kg. The method above was sensitive and accurate to determine DA of ASP in shellfishes.