Three different typical microstructures (lath, equiaxed and duplex microstructures) of Ti-22Al-20Nb-7Ta alloy were obtained by thermomechanical processing. In order to analyze the deformation behavior, the typical microstructures were studied by tensile test and the fracture mechanism was also discussed. The results showed that for equiaxed microstructure, there are three slip transmission modes between O phase and B2 phase, indicating that the two-phases had good deformation coordination relationship. The O phase and B2 phase formed different type dislocation configurations, which is an important deformation strengthening mechanism of the alloy. For duplex microstructure, the fine lath O phase and α2/O phase precipitated in B2 matrix, which enhanced the hindrance effect on dislocation motion. The crack initiation and crack propagation process were observed by in-situ tensile test. For lath microstructure, the coarse lath O phase precipitated near B2 grain boundary, and the crack was easy to generate at grain boundary and rapidly fracture. For equiaxed microstructure, the microcracks were easy to generate in the slip lines and were connected to each other to generate the maincrack by the plastic deformation of B2 phase. For duplex microstructure, the microcracks generated in the lath O phase, the internal of α2/O phase and the phase interface of α2/O phase and B2 phase and were connected to each other to generate the maincrack by the plastic deformation of B2 phase. Because the disordered distribution of α2/O phase and lath O phase, the direction of crack propagation is tortuous.