A helicopter is widely used in forestry disease and pest control. An application tank of helicopter is taken as a loading container of the liquid medicine. It is very necessary for the reasonable anti-shaking structure inside the helicopter medicine tank for the aviation operation stability and energy consumption. In this study, the structural design was optimized to place an anti-shaking grid structure in the inner chamber of the tank, in order to reduce the stability of the helicopter that caused by the shaking of the liquid during operation. Numerical simulations were carried out on the Fluent's Volume of Fluid (VOF) with the Realizable turbulence models. Evaluation indicators were selected as the variation of the free liquid surface waveform and the pressure magnitude at the internal reference point for the variable speed excitation of the pillbox. The maximum flow velocity of liquid was then determined to simulate the liquid sloshing in the empty tank along the excitation direction. The position of the damping grid structure was also determined, according to the formula of energy dissipation of liquid sloshing around the flow resistance. The simulation results show that the maximum pressure at the reference point increased with the increase of the height of the grid. But the time to reach the maximum pressure was similar. Specifically, the liquid slosh frequency was lower at the grid height of 100 mm. The pressure value was smaller at the reference point with the grids number of 9, and then tended to be relatively stable, as the number of grids increased gradually. A medicine tank shaking test bench was constructed to simulate the flight conditions of helicopter operation, in order to verify the anti-shaking effect. The test results showed that the greater the acceleration was, the greater the maximum impact force on the inner wall of the powder cabinet was, and the earlier the maximum impact force time was. The greater the liquid filling rate was, the greater the maximum impact force on the inner wall of the cabinet was. The maximum pressure increased by 27.7% at the liquid filling rate of 0.8, compared with the liquid filling rate of 0.6. There was the consistent shape trend of the free liquid surface under different liquid filling rates. But the time of violent shaking was advanced with the increase of liquid filling rate. At the same time, the tank with the higher liquid filling rate was not susceptible to the secondary impact of the liquid after excitation. Furthermore, the time decreased for the liquid level to stabilize with the gradual increase of the forward tilt angle of the medicine tank under different working conditions. Once the forward tilt angle of the medicine tank changed from 0° to 10°, the time decreased by 44.6% for the liquid level to stabilize. It was the much longer to stabilize, when the medicine tank was tilted, the side of which the lower liquid level was wobbled more violently. A vertical damping grid structure was obtained with a height of 100 mm and a number of 9 grids after optimization of numerical simulation. A comparison of the simulation and test showed that the anti-shaking damping grid structure was effectively reduce the slosh amplitude of the liquid inside the cabinet after excitation. The time was reduced by 54.8% than before from the beginning of sloshing to the liquid level of the empty tank, indicating the better inhibition effect. The experimental design and the reasonable grid structure can provide a strong reference for the subsequent research on the anti-sloshing structure inside the tank of a helicopter.