Ti-6Cr-5Mo-5V-4Al (Ti-6554) alloys with excellent comprehensive properties are expected to become the preferred material for large-scale parts in the aviation field. However, the processing parameters of large-scale parts have a significant impact on the microstructure, so it is necessary to optimize the hot working process to improve the comprehensive mechanical properties of the alloy. In this paper, hot compression experiments of Ti-6554 alloy were carried out in the temperature range from 680 to 830 ℃ and strain rate range from 0.001 to 10 s−1. The hot workability of the Ti-6554 alloy was studied based on the hot processing map and microstructure evolution. The Arrhenius constitutive model of the two phase region and single phase region was established. It was found that the thermal activation energy was higher at high value in the adopted range of strain rate, and the average thermal activation energy gradually decreased with raising the strain. The peak efficiency in the hot processing map occurred at 680 ℃/0.001 s−1 and 770 ℃/0.001 s−1 with efficiency values of 0.47 and 0.48, respectively. The instability regions were mainly concentrated at a high value in the adopted range of strain rate, and the typical instability phenomenon was flow localization. With raising the strain rate and temperature, the volume fraction and average size of the α phase decreased due to the dynamic phase transformation. Dynamic recovery (DRV) was the major deformation mechanism at low temperatures and low strain rates. The deformation mechanism gradually changed to DRX with the increase of temperature and strain rate. However, the increase of temperature at a higher strain rate could not improve the level of dynamic recrystallization (DRX). Based on electron backscatter diffraction (EBSD) characterization, the DRX types of the β phase were determined to be discontinuous dynamic recrystallization (DDRX) and continuous dynamic recrystallization (CDRX). DDRX mainly occurred at high temperatures and low strain rates. Furthermore, the spheroidizing mechanism of the equiaxed α phase was also analyzed. First, under the action of compressive stress, the aspect ratio of the equiaxed α phase gradually increased and became the lamellar α phase. Subsequently, the low angle grain boundaries (LAGBs) gradually changed to high angle grain boundaries (HAGBs), accompanied by wedging of the β phase. Finally, the spheroidization process was completed.