In this paper, the new separation structure (VDWDWC) for separation of a quaternary system is proposed for the first time, which has lower energy consumption and higher separation efficiency than the traditional three-column and Kaibel column. Sensitivity analysis and response surface optimization (RSM) are applied to the structural design and parameter optimization of VDWDWC. In addition, the dynamic control of VDWDWC is also investigated. Specifically, the performances of temperature-composition cascade control (TC-CC) with and without feed-forward ratio control are compared and analyzed. The results suggested that the TC-CC structure can achieve outstanding controllability for VDWDWC, when the feed flow rate and feed composition is disturbed. In particular, TC-CC with feed-forward ratio control has better dynamic response: the maximum deviation was reduced by 53.7%, and the settling times are significantly shortened, while the steady state deviation of product purity was slightly reduced.