The multiplicity of matching between reaction and separation for reactive distillation (RD) process leads to a more complex design of RD column, however, the exploration of coupling problem between reaction and separation for the design of reaction section in the RD column is still a blank of RD research. In this article, a design framework for the reaction section in the RD column based on the reaction equilibrium degree (RED) is demonstrated. The interaction relationship between residence degree and separation efficiency of reaction section is established by means of spline interpolation method. Herein, the synthesis of malonic acid (MA) from dimethyl malonate (DM) hydrolysis, as case study, was investigated to obtain coupling regularities of reaction and separation for specified design targets and further design the reaction section of RD column from principle. The results validated the effectiveness of the proposed framework and provided theoretical guidance for challenging RD process.