Objective A simplified analytical method comprised of solid-phase extraction(SPE) and ultra performance liquid chromatography coupled with negative electrospray ion source tandem mass spectrometry(UPLC-ESI——MS/MS) has been developed for the determination of eleven hydroxylated polybrominated diphenyl ethers(OH-PBDEs) in human blood.Methods The solvent for the mobile phase and the SPE conditions were optimized.Results The recoveries of the OH-PBDEs spiked in human blood relative to internal standards were in the range of 53.2%-117.9% at three spiked levels.The relative standard deviations(RSD) were 4.71%-18.85%.The limits of detection(LOD,S/N=3) was in the range of 0.00886-0.058 9 ng/ml.Conclusion The proposed method is sensitive,accurate,fast,simple,low solvent consumption and suitable for the determination of OH-PBDEs in human serum without derivatization.