Rice straw is waste material from agriculture as a renewable biomass resource, but the black liquor produced by straw pulping causes serious pollution problems. The twin-screw pulping machine was designed by Solidworks software and the straw breakage model was created by the Discrete Element Method (DEM). The model of straw particles breakage process in the Twin-screw pulping machine was built by the Tavares model. The simulation results showed that the highest number of broken straw particles was achieved when the twin-screw spiral casing combination was negative-positive-negative-positive and the tooth groove angle arrangement of the negative spiral casing was 45°−30°−15°. The multi-factor simulation showed that the order of influence of each factor on the pulp yield was screw speed > straw moisture content > tooth groove angle. The Box-Behnken experiment showed that when screw speed was 550 r/min, tooth groove angle was 30°, straw moisture content was 65% and pulping yield achieved up to 92.5%. Twin-screw pulping performance verification experiments were conducted, and the results from the experimental measurements and simulation data from the model showed good agreement.