A single-pass and multi-pass compression experiments with a Ti-6Al-4V alloy fabricated with hot isostatic pressing (HIP) were carried out on a Gleeble-1500D simulator. The true stress-strain curve, microstructure and microhardness of the alloy deformed at a total strain of about 70 % were studied. The results show that the stress value increased as the strain rate increased during each deformation pass and the same was true for the single pass. At the initial deformation stage, the flow stress increased rapidly with the increase in the strain until it reached the peak; then it showed a different softening extent, which was more obvious for the three-pass deformation than for one-pass and two-pass deformation. During the multi-pass deformation, the lamellar α phase was mainly distorted, but during the one-pass and two-pass deformation, it was bent; the spheroidisation of the lamellar α phase mainly occurred during the three-pass deformation, significantly increasing the extent of softening. Meanwhile, the degree of the spheroidized α phase and the volume fraction of β-transformed phase (βt) increased as the strain rates increased. Finally, a tri-modal microstructure, including the β-transformed phase (βt), lamellar α phase and equiaxed α phase was obtained during three-pass deformation. In the process of multi-pass deformation, the microhardness increased with the increase in deformation passes. When the strain rate was 1 s–1, the microhardness increased from 299.5 HV and 309.1 HV to 342.6 HV with the increase in deformation passes. It was also found that the microhardness increased with an increase in the strain rate under a certain amount of deformation.