The hot deformation behavior of as-cast Ti-5553 (Ti-5Al-5Mo-5V-3Cr) alloy with coarse grain was investigated at the temperature range of 700 °C-1100 °C and strain rate range of 0.001 s_^-1-10 s_^-1 by Gleeble-3800 thermal physical simulator. The results show that the flow stress is sensitive to both temperature and strain rate, and the flow curves display various softening modes at different conditions. The activation energy map and constitutive relationship are constructed for the alloy, and the average deformation activation energy is calculated as 447.2 kJ/mol. The hot processing map is successfully established based on the dynamic materials model with the identification of underlying mechanisms at various processing regions. Two peak domains are identified in the hot processing map, which are: 800 °C-975 °C/0.001 s_^-1-0.01 s_^-1 and 1000 °C-1100 °C /0.01 s_^-1-0.1 s_^-1, and the flow instability region locates at the region with strain rate higher than 1 s_^-1. External cracking, adiabatic shear banding and/or flow localization are observed at low-temperature deformation and in the flow instability region, and these conditions should be avoided for actual processing. The mechanism at the peak efficiency domains are DRV or the combination of DRV and DRX, among which the region with the occurrence of extensive DRX is recommended as the optimal processing window for the alloy at high temperature about 1100 °C and medium-low strain rate about 0.01 s_^-1.