This paper developed determination methodology of gas chromatography-tandem mass spectrometry for 17 polycyclic aromatic hydrocarbons of pharmaceutical rubber stoppers to evaluate the safety of residual polycyclic aromatic hydrocarbons. A mixture of acetone-hexane (V丙酮∶V正己烷=1∶1) was used as the extraction solvent, the target substances of rubber stopper were extracted by microwave, and D8-naphthalene, D10-pyrene and D12-benzo[a]pyrene were used as internal standards for quantification analysis. Good linearity was observed within the range of 2-200 ng/mL, the correlation coefficient R was 0.9984-0.9999, and the limit of detection was in the range of 0.35-1.25 ng/g in this methodology. Besides, the recovery ranged from 92.24% to 118.47% (RSD:0.86%-13.23%). The above method was used to extract 17 batches of rubber stoppers from 8 manufacturers on the market, and different polycyclic aromatic hydrocarbons were extracted from them. The detected amount of carcinogenic PAHs was in the range of 0.0004 to 0.1278 μg/g, benzo[α]pyrene from 3 batches of the rubber stoppers were in the range of 0.0013-0.0042 μg/g and the detected amount of unclear carcinogenic PAHs was 0.0004-0.2980 μg/g. This method is accurate, sensitive, simple and suitable for the quantitative determination of the residual high-risk carcinogenic polycyclic aromatic hydrocarbons (above five rings) in rubber stoppers.