Based on enhanced matrix removal lipid column (Captiva EMR-Lipid) purified， a method was developed for determination of 42 kinds of triazine， amide and sulfonylurea herbicides residues in shellfish by ultra-high performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS). After optimizing the pretreatment and chromatographic conditions， acetonitrile， Captiva EMR-Lipid column were used as the extraction solvents and purification agents， respectively. The separation of 42 analytes was performed on a Shim-pack GIST C18-AQ column (100 mm × 2.1 mm， 1.9 μm) with gradient elution. The MS/MS detection was performed with electrospray ionization in positive ion mode and multiple reaction monitoring mode. The 42 analytes showed great linear relationships in the range of 0.2-20 μg/L with correlation coefficients (R2) all above 0.992. The limits of detection (LODs) were 0.2-0.4 μg/kg and the limits of quantitation (LOQs) were 0.5-1.0 μg/kg. The average recoveries of analytes varied from 61.0% to 110.3%， and the relative standard deviations (RSDs) were between 0.1% and 17.4%. Using the established determination method， 23 shellfish samples were detected， and 5 kinds of herbicides residues were detected. The method was simple， rapid， high accurate and sensitive， which was suitable for the simultaneous determination of 42 kinds of herbicides residues in shellfish.