In order to study the influencing factors of residual stress of the Ti-6.5Al-1Mo-1V-2Zr powder laser shaping substrate, 19 samples were formed with different process parameters, and then an indentation method was used to measure their residual stress. The effects of the laser power, the powder feeding rate, the laser scanning speed, the number of shaping layers and the angle of laser scanning on the substrate residual stress were summarized. The results show that the substrate residual stress is increased with the increase of the laser power. However, the stress begins to decrease when the laser power is larger than 1700 W. When the powder feeding rate range is from 0.5 to 1 g/min or from 1.5 to 2 g/min, the residual stress decreases with the increase of the powder feeding rate. But when the powder feeding rate is between 1 similar to 1.5 g/min the residual stress increases with higher powder feeding rate. In addition, with the increase of the scanning speed the substrate residual stress increases and then decreases. The residual stress of the substrate decreases with the number of layers increasing. To the samples with different scanning angles, the residual stress of the substrate is smaller at 60 scanning angle than at other scanning angles, while the maximum value of the substrate residual stress occurs at 30 degrees.