Carbon capture, utilization, and storage (CCUS) is a technique to curb carbon dioxide (CO2) emissions from significant point sources. CO2 separation is the first stage in the CCUS. Cryogenic CO2 separation is the emerging method of separating CO2 from different sources. Plate-fin heat exchanger (PFHE) is one of the compact heat exchangers generally used in cryogenic applications. Due to its advantages, it is also used in the cryogenic CO2 separation process. In this analysis, a PFHE is designed and analyzed by using an analytical method and Aspen software, and the results are compared. In the analytical design, the Maiti and Sarangi correlations are considered. The effect of the change in the thermos-physical properties on the volume and cost of the heat exchanger (HX) is analyzed. The energy penalty to separate CO2 from a CO2/N2 gas mixture with a 30% CO2 concentration is observed to be 1.063 MJ/kg of CO2. The volumes of HXs “A” and “B” determined by the analytical approach are found to be around 0.323 m3 and 0.978 m3, respectively. The volumes of HXs “A” and “B” by the Aspen EDR approach are found to be around 0.239 m3 and 0.839 m3, respectively.