Using first principles, we theoretically investigate the strain manipulation of the ultrafast spin-flip processes on the Ni@B80 endohedral fullerene by using highly correlated quantum chemical calculations. It is shown that the ultrafast local spin flip on Ni@B80 can be achieved via Λ processes with high fidelities in both the equilibrium and distorted structures. Moreover, the applied strain on Ni@B80 can significantly lead to the redistribution of spin density, and therefore dominate the spin-flip processes. It is interesting that the strain effects on the spin-flip processes of Ni@B80 are not identical. Specifically, when a strain is applied along the direction across the Ni atom, the influence is exactly opposite to the case when the strain direction goes without crossing the Ni atom. This orientation-dependent strain effect is also demonstrated by analyzing the modulated energy gaps between the singly occupied molecular orbital (SOMO) and the lowest unoccupied molecular orbital (LUMO) of the system. The present results shed some light on the mechanical control of the magneto-optic dynamics behavior of the endohedral fullerenes, and further provide the idea that strain engineering and spin engineering can be combined for the design of nanoscale magnetic storage units and spintronic devices.