The Ti₂AlNb alloy was joined with TC4 alloy by vacuum diffusion bonding. The relationship between bonding parameters, and joint microstructure and shear strength was investigated. The results indicated that the diffusion of Al, Ti, Nb and V elements across bonding interface led to the formation of three reaction layers: B2/β layer and α₂ layer on the TC4 side, and α₂+B2/β layer on the Ti₂AlNb side. The bonding temperature determined the atomic activity, thus controlling the growth of reaction layers and influencing the shear strength of the joint. When the Ti₂AlNb alloy and TC4 alloy were bonded at 950 °C for 30 min under 10 MPa, the shear strength of the joint reached the maximum of 467 MPa. The analysis on the fracture morphology showed that the fracture occurred within the B2/β layer and the fracture model was ductile rupture. Meanwhile, the formation mechanism of the Ti₂AlNb/TC4 joint was discussed in depth.