In order to understand further the micro-mechanism of helium bubble punching out of the dislocation loop in α-Fe, it is necessary to study the ultimate pressure characteristics of helium bubble punching out of the dislocation loop. In this paper, a cubic representative volume element (RVE) model of the metal-helium bubble is established. For eight types of spherical helium bubbles with different initial radii, molecular dynamics simulations are carried out with the initial helium-to-vacancy ratio serving as a variable and the ultimate pressure of helium bubble and the critical helium-to-vacancy ratio at the beginning of dislocation loop formation in each model are obtained. The results show that for helium bubbles with dimensionless radius ranging from 2 to 10, both the ultimate pressure and the critical helium-to-vacancy ratio of helium bubble punching out of the dislocation loop decrease nonlinearly with the increase of initial helium bubble radius. The relationships of the ultimate pressure and the critical helium-to-vacancy ratio with the initial radius of helium bubble are fitted respectively according to the simulation results and the fitted two equations are in good agreement with the results of previous theoretical studies. The critical helium-to-vacancy ratio required for helium bubble punching out of the dislocation loop in α-Fe has an obvious size effect. For the helium bubble in the late nucleation stage (e.g. helium bubble with an initial radius of 0.81 nm) and non-ideal gas stage (e.g. helium bubble with an initial radius ranging from 1.00 nm to 2.50 nm), the critical helium-to-vacancy ratios for punching out of the dislocation loop are the same as the initial helium-to-vacancy ratio corresponding to the peak pressure point of helium bubble. But for early or middle nucleation stage, such as helium bubble with an initial radius of 0.50 nm, the critical helium-to-vacancy ratio for punching out of the dislocation loop is about 13.46% greater than the initial helium-to-vacancy ratios corresponding to the peak pressure points. At the initial moment (0 ps), in the cross section passing through the center of cubic RVE, the shear stress is concentrated, and the maximum shear stress of Fe atom array around the helium bubble is located at the intersection points (i.e. at 45°) of diagonal and helium bubble boundary, and it is distributed symmetrically with respect to the double fold lines of the cross section parallel to the sides. Both the range of shear stress concentrating area and the maximum shear stress increase with the initial helium-to-vacancy ratio increasing. The dislocation loop’s punching direction corresponds to the direction of the maximum shear stress. The research in this paper can deepen the understanding of the physical properties of helium bubbles in metals and lay a useful foundation for the subsequent analyzing of the effects of helium bubbles on the macroscopic physical and mechanical properties of materials.