A novel method was developed to detect four lipophilic shellfish toxins (OA, SPX1, DTX1, and AZA1) in edible shellfish products via a combination of QuEChERS technology and high performance liquid chromatography-tandem Mass Spectrometry (HPLC- MS/MS). The samples were homogeneously extracted with acetonitrile-water (85%, V/V) and purified with QuEChERS technology. Using C18 column with acetonitrile/water (2 mmol/L ammonium acetate, 0.1% formic acid) as mobile phase, the analytes were separated by HPLC-MS/MS with electrospray ionization (ESI) mode, followed by multiple reaction monitoring (MRM). Quantification was performed by external standard calibration method．The limits of detection (LOD, S/N=3) for OA and DTX1 were 10 μg/kg, the calibration curves showed good linearity in the range of 1.0 to 100 μg/L, while the LOD for AZA1 and SPX1 was 1.0 μg/kg, with a linearity range between 1.0 20 μg/L. The correlation coefficients (r2) were > 0.999 for all four toxins. The average spiked recoveries of the shellfish toxins at three concentration levels were between 81.9% and 93.1% while relative standard deviation (RSD) was < 5%. A total of 15 import and export samples of fish including mussels, octopus, geoducks, and oysters were screened by this newly developed method and SPX1 toxin was found in 5 samples. This method is quick, easy-to-perform, sensitive, and appropriate to detect lipophilic shellfish toxins in shellfish products.