Abstract: For rapidly and sensitively determining the acrylamide in mainstream cigarette smoke, a liquid chromatography-electrospray ionization tandem mass spectrometric (LC-MS/MS) method was developed, in which mainstream cigarette smoke was collected by Cambridge filter pad, then extracted by deionized water and diluted by acetonitrile. The acrylamide in mainstream smoke of domestic and imported cigarettes with different tar deliveries was determined. The results showed that:1) The samples of mainstream cigarette smoke could be analyzed directly after extraction by deionized water and dilution by acetonitrile, the analysis operation only took five minutes. 2) The detection limit of acrylamide was 0.15 ng/mL and the recovery ranged from 94.27% to 97.92%. The intra-day and inter-day precisions were less than 6% and 10%, respectively. This method is simple, rapid, accurate, and suitable for the determination of acrylamide in batches of mainstream cigarette smoke samples.