Abstract: A simple, sensitive and robust method for determination of 4(methylnitrosamino)-1-(3-pyridyl)-1-butanone （NNK） in mainstream cigarette smoke by gas chromatography-tandem quadrupole mass spectrometry (GC-MS/MS) was developed. Four kinds of tobacco specific nitrosamines (TSNAs) exist in cigarette smoke, NNK is considered as one of the most harmful compounds in cigarette smoke. Determination of NNK in mainstream cigarette smoke is a challenging task to analytical chemists . GC-TEA method for the determination of NNK was often involved with complex clean-up steps. In this paper, the mainstream cigarette smoke collected on Cambridge pad was extracted by dichloromethame and the extra was cleaned up by basic alumina Solid column cartridge then analysed by GC-MS/MS. The reproducibility, recovery and detection limit of the method were desirable. The method was suitable for the determination of NNK in mainstream cigarette smoke. Column packing and concentration work are omitted in the total sample process. The use of deuterated internal standard simplifies the calibration work and brings a more accurate result. A comparison experiment with GC-TEA and the recovery experiment demonstrate the accuracy of this method.