Abstract: The oyster sample (2.00 g) was extracted with methanol twice (10 mL each time). MgSO₄ (1 g) was added in the combined supernatant for water removal and C₁₈ solid phase extractant (150 mg) was added for purification. LC-high resolution MS was applied to the determination of 6 lipophilic shellfish toxins in the sample solution with QuEChERS. Hypersil GOLD C₁₈ chromatographic column was used as stationary phase, and the mixture of acetonitrile and 2 mmol·L^-1 ammonium formate solution containing 0.2% (φ) formic acid mixed in different ratios was used as mobile phase in gradient elution. ESI, primary full scan and data dependent secondary scan mode were adopted in high resolution MS. Linear relationships between values of peak area and mass concentration of the 6 lipophilic shellfish toxins were kept in definite ranges, with detection limits (3S/N) in the range of 0.2-0.8 μg·kg^-1 and lower limits of determination (10S/N) in the range of 0.6-2.8 μg·kg^-1. On the base of blank oyster sample, test for recovery was made by standard addition method; values of recovery found were in the range of 81.1%-108%, with RSDs (n=6) of determined values in the range of 2.8%-12%.