The widespread application of titanium alloy materials in aerospace structural design makes them susceptible to thermo-vibration coupling fatigue failure in harsh vibration and thermal environments. Vibration fatigue issues significantly affect the safety and operational reliability of aircraft. In order to obtain optimal design details for titanium alloy welding structures under thermo-vibration coupling conditions, experimental specimens with different structural details of TC4 titanium alloy welding structures were designed to simulate actual structural designs. The structural details included skin with U-shaped supports at different angles, skin with L-shaped supports, and skin with T-shaped supports. A thermo-vibration coupling vibration fatigue test system was established, and vibration fatigue tests were conducted at a temperature of 150°C. All structural fatigue crack failures occurred at the welds. The experimental results were statistically analysed, and using the Chauvinet criterion, abnormal data points were removed. The influence of structural details on vibration fatigue life was determined through F-tests. It was found that for the skin with a U-shaped support structure, a support angle of 90° resulted in a longer vibration fatigue life. When comparing skin with T-shaped support and skin with L-shaped support structures, the T-shaped support structure exhibited a longer vibration fatigue life. Among the three structural types, the skin with a T-shaped support structure has the longest vibration fatigue life. These experimental conclusions serve as important references for the design of thin-walled structures in aircraft structural design.