As a new solid-state welding process, friction stir welding (FSW) has been successfully used for joining low melting point materials such as aluminum and magnesium alloys, but the FSW of high melting point materials such as steels and titanium alloys is still difficult to carry out because of their strict requirements for the FSW tool. Especially for the FSW of titanium alloys, some key technological issues need to solve further. In order to accomplish the FSW of titanium alloys, a specially designed tool system was made. The system was composed of W-Re pin tool, liquid cooling holder and shielding gas shroud. Prior to FSW, the Ti-6Al-4V alloy plates were thermo-hydrogen processed to reduce the deformation resistance and tool wear during the FSW. Based on this, the thermo-hydrogen processed Ti-6Al-4V alloy with different hydrogen content was friction stir welded, and the microstructural characterizations and mechanical properties of the joints were studied. Experimental results showed that the designed tool system can fulfill the requirements of the FSW of titanium alloys, and excellent weld formation and high-strength joint have been obtained from the titanium alloy plates.