The work aims to study the erosion mechanism and law of gas-solid two-phase flow on the manifold for relief pressure of high-yield natural gas well. During the study of the erosion of manifold for relief pressure by CFD software, Reynolds average Navier-Stokes (RANS) equation was used to obtain the gas phase motion state. The particles tracks were captured by the discrete phase model (DPM). Then, the Oka erosion model was used to study the relationship between the five factors such as the angle of the elbow, the position of the elbow, and the discharge volume and the erosion law of the pipe wall. Finally, the maximum erosion rate, wall quality loss and pipeline puncture time were used to evaluate the erosion of manifold for relief pressure. Under the premise of controlling the single factor variable, as the percentage sand increased from 1% to 5%, the maximum erosion rate of the elbow increased by about 4 times. When the discharge volume increased from 3.0×105 m3/d to 5.1×106 m3/d, the maximum erosion rate appeared near 1.0×106 m3/d approximately, which increased by 3.7 times compared with 3.0×105 m3/d. When the bend angle increased from 90° to 165°, the maximum erosion rate declined by 85%. The maximum erosion rate of elbow at 120° is the largest. As the distance from the elbow to the outlet increased from 5 m to 30 m, the maximum erosion rate decreased by 86%. When the particle shape factor increased from 0.67 to 1, the maximum erosion rate increased by 5 times. The correlation between sand content and maximum erosion rate is the greatest, while the correlation between the position of the elbow and the maximum erosion rate is the smallest. The maximum erosion rate increases with the increase of percentage sand and particle shape coefficient, and decreases with the increase of elbow angle and straight pipe length from outlet. However, the maximum erosion rate of the elbow pipe at 120° is the largest; with the increase of the discharge volume, the maximum erosion rate of the elbow increases firstly, next decreases, and ultimately stabilizes.