Abstract: Titanium/steel composite components by diffusion welding have a broad application prospect in advanced aerospace manufacturing. The IMCs are the main reason for the deterioration of the joint performance. AlCoCrNiCuAg high-entropy alloy powder interlayer with liquid phase separation was designed. By forming parts of the liquid phase, the adverse influence of single plastic deformation on the microstructure and mechanical properties of the interface was reduced. The effect of AlCoCrNiCuAg high-entropy alloy powder interlayer on the interfacial microstructure and mechanical properties of the joints between TC4 titanium alloy and 316L stainless steel by diffusion welding at different temperatures was investigated. The results show that the typical interfacial microstructure of the joints is α-Ti + β-Ti/β-Ti/β-Ti + Ti(Fe,Ni) + Ti₂Ni/Ti(Fe,Ni)/TiFe₂ + Fe₂Cr₅Ti₁₇/ Fe₂Cr₅Ti₁₇ + λ-(Fe,Cr)₂Ti + α-Fe/γ-Fe. As the welding temperature increases, the thickness of Ti(Fe,Ni) and α-Fe adjacent to the TiFe₂ reaction layer increases, and the defects at the joint pores are reduced. The shear strength of the joints by diffusion welding exhibits an increasing trend under the synergistic action, and the highest shear strength reaches 181 MPa at 1 010 °C for 30 min. The high-entropy alloy powder interlayer inhibits the generation of TiFe₂ and other brittle IMCs and promotes the formation of the (Fe,Ni) solid solution phase, achieving a sound bonding between titanium and steel.