It is an important issue for the optimization design and refined control of extrusion process of large-diameter hard wrought alloy profiles to reveal the effects of forming parameters on the process and to determine the reasonable range of each forming parameter. And it’s also significant for the R&D, debugging and application of the large tonnage (such as 200 MN) extrusion press. Therefore, we developed an applicable and reliable FE model for the needle piercing extrusion process for Inconel690 alloy large-diameter thick-walled tube (Ф420 mm×60 mm) under the DEFORM-2D software environment. And the effects of forming parameters (i.e. extruding ratio λ, die taper angle α, sizing belt length h, billet initial temperature T and ram speed v) on the peak temperature of billet Tmax, the peak damage of billet Dmax, the uniformity of flow rate at die export Fsdv and the peak extrusion load Lmax were investigated using virtual orthogonal experiment based on the developed FE model. The results show that the order of forming parameters’ significance to Tmax, Dmax, Fsdv and Lmax are T>v>λ>h>α, α>v≈λ>T>h, h>v>T>α>λ, and λ>T>α>v>h, respectively. Comprehensively considering the quality of the extruded tube and the extrusion load, we pointed out that the reasonable ranges of forming parameters are as follows: λ=5.74~6.37, α=35°~45°, h=60~120 mm, T=1080~1180 °C, and v=150~250 mm/s.