To improve the plastication performance of high-nitrogen single-base gun propellant and determine appropriate process parameters for high-nitrogen nitrocellulose （NC） during continuous twin-screw plastication， Molecular dynamics simulation was employed to analyze the effects of ethanol-ether ratio and solvent-NC ratio on NC plasticization. Ethanol-ether solubility experiments and rheological tests of the plasticized material were conducted to verify the simulation results. Results show that the solubility parameter of the ethanol-ether mixed solvent closely matches that of high-nitrogen NC. Strong hydrogen-bonding and electrostatic interactions exist between high-nitrogen NC and ethanol， while van der Waals forces dominate between NC and ether. At an ethanol-ether ratio of 1∶1.4， ethanol forms strong hydrogen bonds with NC， resulting in higher solubility， which is in good consistency with the experimental results that NC exhibits maximum solubility at an ethanol-ether ratio of 1∶1.36. Increasing the solvent-NC ratio within a certain range weakens the intramolecular hydrogen-bond interaction of NC and increases the radius of gyration of the molecular chains. These changes are correlated with the macroscopic phenomena of reduced shear viscosity of the material and a more compact and uniform extruded strands surface. At a solvent-to-NC ratio of 0.85， NC exhibits the largest radius of gyration for NC （22.4 nm） and the fewest intramolecular hydrogen bonds， which aligns with the experimental result that the apparent shear viscosity of the material is minimized at a solvent-NC ratio of 0.825. Due to the combined effects of strong screw shear and solvent volatilization， it is recommended to use a lower screw speed when plasticizing high-nitrogen NC with the simulated solvent-NC ratio. Additionally， appropriately increasing the screw speed under a low solvent-NC ratio can also effectively reduce material viscosity， attention must be given to the potential adverse effects caused by shear-induced heating.