A comprehensive analytical method based on gas chromatography-mass spectrometry (GC-MS) has been developed for the simultaneous determination of 8 polybrominated biphenyl congeners (PBBs: BB-15, 18, 52, 101, 153, 180, 194 and 206) in human serum. After the protein was removed, the sample was cleaned-up by an Oasis HLB solid-phase extraction (SPE) cartridge, then purified further by a two-layer cartridge containing activated silica gel and a mixture of silica gel and sulfuric acid, in which elution solvent was optimized. The eluent was evaporated to about 100 microL by a gentle nitrogen stream for GC-MS analysis. The separation was performed on a DB-5ms column (15 m x 0.25 mm x 0.1 microm) and the qualitative and quantitative analyses were carried out in electron impact (EI) selected ion monitoring (SIM) mode, in which isotope was used as internal standard. The limits of detection (LODs, 3.14 times of standard deviation) and the limits of quantification (LOQs, 10 times of standard deviation) were 0.002-0.029 ng/mL and 0.008-0.092 ng/mL respectively for the 8 PBBs. The average recoveries for all PBBs at three spiked levels were 74.24%-119.49% with the relative standard deviations in the range of 1.23%-12.02%. The method was verified by accurate analysis of BB-153 in organic contaminant standard reference materials (SRM) 1957 and 1958. This method is simple, rapid, accurate, precise and fit for the determination of PBBs in human serum.