Abstract：A multi-residue method based on high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) was developed for the quantitative determination of hexabromocyclododecane (HBCD) and tetrabromobisphenol A (TBBPA) in bivalves. The target analytes were extracted with the mixture of hexane and dichloromethane ( 1∶1, V/V). Then the co-extracted lipid was removed by sulfuric acid treatment．The newly obtained extract was cleaned up with silicone solid phase extraction column. The analytes were separated on a Thermo Hypersil Gold C18 column by gradient elution with water as mobile phase A and methanol-acetonitrile as mobile phase B, and detected by multiple reaction monitoring (MRM) with electrospray ionization (ESI) under negative ion mode. And the quantitative results were calculated by the internal standard method. The results showed that the calibration curves were linear (R2>0.995) in the concentration range of 0.5~100 ng/mL for HBCD and TBBPA. The limits of quantitation for HBCD and TBBPA were 0.05 μg/kg. The average recoveries at three spiked levels ranged from 70.5% to 92.4%. Intra-day and inter-day relative standard deviations (RSDs) were 3.4%-9.1% and 6.3%-10.2%, respectively.