Abstract: A method for the simultaneous determination of tetrodotoxin (TXT) and microcystin-leucine arginine (MC-LR) contents in shellfish from eastern Fujian by using the direct dilution combined with the ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) was established. TTX and MC-LR in shellfish were extracted with 1% acetic acid-90% methanol aqueous solution, and diluted with 0.5% acetic acid methanol. TTX and MC-LR were separated by using the Acquity HILIC hydrophilic chromatographic column and Shim-pack GIST C18-AQ HP reversed chromatographic column, respectively. The acetonitrile-0.1% formic acid aqueous solution was used as the mobile phase for the gradient elution. And the UPLC-MS/MS analysis was performed and quantified by using the matrix-matched standard curve of external standard method. The detection limits of TTX and MC-LR were 10 μg·kg^-1 and 5 μg·kg^-1, respectively, and the limits of quantitation were 30 μg·kg^-1 and 15 μg·kg^-1, respectively. The standard supplemental levels of the two toxins were 50 μg·kg^-1, 100 μg·kg^-1, 500 μg·kg^-1 (calculated by fresh weight). The range of the recovery rates was 84.0%-97.6% and 85.5%-92.2%, respectively, with the relative standard deviations (RSD,n=6) were 5.3%-10.0% and 6.9%-7.6%, respectively. The method was accurate and reliable, which was suitable for the simultaneous determination of tetrodotoxin (TXT) and microcystin-leucine arginine (MC-LR) in shellfish in eastern Fujian.