The invention discloses a new production process of a large seamless steel pipe. The process comprises the following steps: pipe billets are preheated to the temperature of 1050-1290 DEG C by a heating furnace, and delivered to a three-roll skew rolling piercing mill for piercing by a skew roll table conveying mechanism to finish diameter expansion and wall reduction rolling, the maximal ratio of diameter to wall D/S is over 32, and hollow billets are produced; the hollow billets are delivered to a three-roll skew rolling elongating finishing mill by a shift oblique orbit conveying mechanism to finish diameter expansion and wall reduction rolling or diameter reduction and wall reduction rolling, and the pierced billets are rolled, straightened, cropped end, cut to length, defect are detected, and the finished products are obtained after passing inspections. The new production process also perfects and improves the conventional three-roll skew rolling seamless steel pipe process, solves the problems of not rolling thin walls and great extension in the three-roll skew rolling process, the diameter expansion and wall reduction rolling can be carried out, and the diameter reduction and wall reduction rolling can be carried out. The new production process is especially suitable for rolling large and oversized seamless steel pipes (Phi is 500-2000mm), the ratio of single reduced diameter and expanded diameter is more than 30%, the reduced wall diameter is more than 70%, and the reduced wall thickness is 5-7 times of that of a longitudinal pipe rolling mill.