Abstract: This article introduces the establishment of an ICP-oaTOF-MS (Orthogonal Acceleration Time-of-Flight Mass Spectrometry) method for the determination of heavy metals, including As, Cd, Hg and Pb, in over 21 kinds of tobacco in a certain province. The samples were digested in a closed-vessel by microwave. Factors affecting the determination were studied in detail, such as sampling quantity, digestion solvent, working parameters for mass spectrometry, calibration curve, detection limit, recovery and precision tests of the method. The optimum conditions for the determination were tested and are discussed in this paper. For all of the analyzed heavy metals,the correlative coefficients of the calibration curves were over 0.9998. The recovery rates were 91.49%-106.25%, relative standard deviations (RSD) were lower than 2% and detection limits were 0.093-0.168 μg/L. Under the given analytical conditions, the contents of the four elements of the same cultivars and stalk positions varied significantly among different locations. The contents of As, Pb, Cd and Hg had ranges of 0.503-1.737 mg/kg, 1.826-4.969 mg/kg, 0.656-2.641 mg/kg and 0.042-0.584 mg/kg, respectively. The contents of As and Hg have some small differences, however, the contents of Pb and Cd are significantly different. Compared with other methods, this method is simple, fast and accurate with a high sensitivity. Sample contents are preferably measured in the ng/L range. Therefore, this method can be used in heavy metal detection and quality control for tobacco which is significant to be able to determine the condition of abundance or deficiency for tobacco, and identify the quality of cigarette production.