The invention discloses a Lagrange puff atmospheric diffusion simulation method in nuclear accident off-site consequence evaluation. A Lagrange mesoscale atmospheric diffusion puff mode is used for calculating the concentration and the dosage of gaseous radioactive materials in each grid point of an evaluation area, and a land-surface and inhomogeneous unstable change meteorological condition of a medium complex degree can be favorably processed. On an appointed grid, one series of Gaussian puff is released to simulate the change of nuclide along with time, and the accident situations of a plurality of releasing points can be simulated in the same time period. The method cites the calculation of aspects including diffusion parameters related to stability, plume rise, thermal inversion layers, ground reflection, dry and wet source item depletion and the like; and under a complex topographic condition, puff division is adopted to process a puff furcation problem, and a mesoscale simulation result more approaches to a practical environment condition. By use of the method, the instantaneous concentration of the nuclide in near ground air, time integral air concentration, ground deposition concentration, smoke plume, the [Gamma] dosage rate of ground deposition and the like can be calculated.