Abstract: A gas chromatography-mass spectrometry (GC-MS) method was successfully developed and validated for simultaneous determination of five Volatile Origanic Compounds (VOC: 1,3-butadiene, isoprene, acrylonitrile, benzene and toluene) in cigarette gas-phase mainstream smoke. Before smoking, each impinger was spiked with D6-benzene internal standard solution. The gas-phase mainstream smoke was trapped by two impingers filled with methanol cool solution. And then, five VOCs were analyzed by GC-MS under selected ions recording mode. The limit of detection and limit of quantification for each VOC were varied from 0.01 to 0.81 μg/cig and 0.04 to 2.73 μg/cig. Recoveries were in the ranged of 92.3% to 98.5% and intra- and inter-assay precision (RSD%) were 1.95 to 9.21. This new VOCs determination method provided higher sensitivity, specificity, and repeatability than earlier methods. Five VOCs levels of 38 commercially available domestic and overseas cigarettes were determined under ISO (International Organization for Standards) and Canadian intense smoking regime by the proposed method. VOCs levels in mainstream smoke under Canada intense smoking regime were twice higher than ISO regime.