The residue hydrotreating process plays a significant role in the petroleum refining industry. In this process, modeling and simulation have critical importance for process development, control, and optimization. However, there is a lack of relevant reports of plant scale due to complexity in characterizing feedstock and determining reaction mechanisms. In this paper, reaction and fractionation models are constructed and simulated for a real-life industrial residue hydrotreating process based on Aspen HYSYS/Refining. Considering the heavier and inferior residue, analytical characterization is carried out for feedstock characterization based on laboratory analysis data. Moreover, two reactor models with parallel structures are proposed to implement the intricate reaction network, namely, a hydrocracker reactor and a plug flow reactor. The former simulates lighter petroleum hydrotreating based on the built-in reaction network. The latter emulates the conversion of a peculiar, heavier resin and asphaltene, using a six-lump model, which expands the scope of the feedstock and improves the accuracy of the model. To obtain a realistic simulation of fractionation, the database-based delumping method is adopted to model it with proper pseudo-components. The simulation results, including temperature rise, hydrogen consumption, temperature distribution, product yield, product properties, indicate that the model is capable of reflecting the realistic process accurately.