Multi-component alloys are emerging as promising metallic materials for cryogenic applications for their excellent combination of high ultimate tensile strength and good ductility. But their low yield strength can severely limit their applications. Lattice distortion is emerging as a feasible method in overcoming this dilemma. Here, we investigate the mechanical and microstructural responses of a high-strength ternary equiatomic medium entropy FeCrNi alloy at 293 K and 15 K using integrated theoretical simulation and experimental efforts centered around in situ neutron testing, first principal calculation, and dislocation-based strengthening models. At 293 K, the yield strength of the alloy is 651±12 MPa, with total elongation of 0.48±0.05. At 15 k, the yield strength increased to 1092±22 MPa, but the total elongation dropped to 0.18±0.01. The single-crystal elastic moduli and macroscopic moduli were determined by in situ neutron diffraction, compared with first-principles calculation. The strengthening contribution to the yield strength from the lattice distortion was calculated based on the Varenne-Luque-Curtine solute strengthening theory for multi-component alloys, which almost doubled from 316 MPa to 629 MPa when decreasing the deformation temperatures from 293 K to 15 K. Dislocation multiplication was found to be the dominant deformation mechanism at both temperatures, whereas no twinning neither phase transformation was observed during deformation according to the in situ neutron diffraction and post-mortem characterization. Accumulated strengthening effects from lattice friction, grain boundaries, and dislocations were calculated and compared with the measured flow stress at both temperatures. These findings reveal the significant strengthening effect of lattice distortion and dislocations, paving the way in designing new multi-component alloys with the superb mechanical performance of cryogenic applications.