Hot isostatic pressure diffusion bonding experiments were conducted on the dissimilar alloys of TC4 titanium alloy and Al6061 aluminum alloy. The interface characteristics, formation mechanism, and mechanical properties of the TC4/Al6061 joint were investigated, and the relevant experiment phenomena were explained by thermodynamic analysis. Results show that obvious mutual diffusion of elements occurs on both sides of base material after hot isostatic pressure diffusion bonding and subsequent annealing treatment. The chemical potential driving force leads to the enrichment of Si and Mg elements in the diffusion transition zone and Al side interface, respectively. The intermetallic compounds, including TiAl₃, TiAl, and Ti₃Al, are formed through metallurgical reactions at the joint interface. The calculation results through effective heat formation model indicate the preferential formation of TiAl₃ phase. The hardness test indicates that the Ti-Al intermetallic compounds formed at the interface exhibit higher hardness. The tensile test reveals that the maximum tensile strength of joint reaches 144 MPa.