The design and optimization of the separation process of acrylic acid and corresponding esters in formaldehyde aqueous solution was systematically researched in this work. Thermodynamics was provided for formaldehyde, acrylic acid, and corresponding esters system according to the particularly. On basis of the thermodynamics, optional separation sequence and separation technology were designed, which reduced separation complexity and search scope. In addition, system integration including process optimization and energy integration were optimized in detail in the procedure. The proposed systematic procedure was applied to acrylic acid and corresponding esters production using methyl acetate and formaldehyde as raw materials. The systematic procedure provided a significant guidance for the separation of the formaldehyde, acrylic acid, and corresponding esters.