Thermo-hydrogen process (THP) has been an important research direction of the titanium alloy heat treatment process. However, the effect of THP on the thermal deformation behavior and microstructure evolution of TC17 alloy during hot compression has not been investigated. In this study, a series of isothermal compression experiments were carried out on hydrogenated TC17 alloy specimens in the temperature range covering the α+β phase region and β phase region of TC17 alloys with different hydrogen contents, to investigate the effect of hydrogen on the high-temperature flow behavior and microstructure evolution. The results show that the primary α phase of the hydrogenated TC17 alloy is significantly reduced. Observing the XRD pattern, the substitutional solution effect of hydrogen causes the β phase lattice to expand, resulting in a shift of the β phase toward a small angle as the hydrogen content increases. The flow stress shows a tendency to decrease and then increase with increasing hydrogen content. This is attributed to the softening effect of hydrogen on the α phase and the hardening effect on the β phase. This also leads to the deformation activation energy showing the same trend. When the hydrogen content increases to 0.4 wt%, the activation energy decreases to the lowest point by about 24 %. Finally, the appropriate hydrogen concentration can effectively reduce the destabilization region in the hot working map and expand the processing window of TC17 alloy.