The deformation behavior of isothermally compressed Ti–6Al–4V alloy in the deformation temperature range from 1093K to 1303K, the strain rate range from 0.001s −1 to 10.0s −1 and the height reduction range from 20% to 60% has been investigated in depth. Effect of the strain on the flow stress, the grain size and the apparent activation energy for deformation of isothermally compressed Ti–6Al–4V alloy is analyzed. The results show that the apparent activation energy for deformation and the grain size of isothermally compressed Ti–6Al–4V alloy in the α+β two-phase region vary slightly with strain: the activation energy increases with strain after an early drop as the primary α grain size varies with strain. On the other hand, the apparent activation energy for deformation of isothermally compressed Ti–6Al–4V alloy in the β single-phase region increases firstly with the increasing of strain and then does that slightly in the strain range from 0.3 to 0.7. A processing map of the isothermally compressed Ti–6Al–4V alloy is constructed at a strain of 0.6. The processing map of isothermally compressed Ti–6Al–4V alloy exhibits that the optimal processing parameters are the deformation temperature of 1143K and the strain rate of 0.001s −1 . Meanwhile, two instability domains in the processing map of isothermally compressed Ti–6Al–4V alloy are as follows: one is in the deformation temperature range from 1093K to 1183K and the strain rate range from 0.011s −1 to 2.02s −1 , and another is in the deformation temperature range from 1243K to 1303K and the strain rate range from 1.0s −1 to 10.0s −1 .