By employing the EXTRACT module in Aspen Plus Software with the aid of selected PSRK equation from our previous work [W. Li, P. Du, F. Cao, W. Ying, D. Fang, Simulation and optimization of the extract segment of solvent deasphalting plant, Computers and Applied Chemistry, 26 (2009) 455–460] [18], this work simulated a solvent deasphalting (SDA) process with mixed C4 solvent and the feedstock of vacuum residue (VR) obtained from a mixed crude oil (Zhongyuan oil:Tahe oil:Changqing oil:Oman crude oil:Zafiro crude oil = 35:5:2:40:18, wt/wt). The feed of VR was lumped as paraffinic, primitive and aromatic components according to their calculated KUOP values. The relative errors not more than 3.94% illustrated the simulated results are comparable with the industrial data for both feedstock (VR and mixed C4 solvent) and products (deasphalted oil—DAO and deoiled asphalt—DOA). The DAO yield was predicted to reduce to 47.2% from 58.0% with increasing temperature of mixed C4 solvent from 100 to 120 °C under operating model-I, but increased from 51.6% to 56.1% with solvent–VR ratio up to 6.5 from 4.5. In addition, a heavier mixed C4 solvent would facilitate remarkable improvement of DAO yield but deteriorate its quality.