The work aims to improve the precision and accuracy of the determination of potassium in cigarette paper by inductively coupled plasma mass spectrometry with dynamic reaction cell (DRC-ICP-MS), identify and master the key factors, and implement effective monitoring and improvement. The main sources of uncertainty were analyzed by the cause-and-effect diagram, the components of uncertainty were evaluated scientifically by the mathematical model, and the expanded uncertainty was proposed according to JJF 1059.1—2012 “Evaluation and Expression of Uncertainty in Measurement”. The results demonstrated that the components of uncertainty were in the range of 0.0067 to 0.0402. The influences on determination results were standard solution preparation, moisture content of sample, sample repeated measurement, calibration curve fitting and sample preparation on the basis of the weights of various components of uncertainty. When the potassium in cigarette paper sample was 13.337 mg/g, the expanded uncertainty was 1.218 mg/g (k=2, P=95%). In conclusion, the uncertainty can be reduced by optimizing the standard solution preparation. Furthermore, the stability of the instrument can influence the uncertainty simultaneously. Therefore attention should be paid to the instrument status closely.