Heat exchangers used as charge air coolers are repeatedly subjected to thermal strain, which may cause fracture. To predict the durability of heat exchangers, stress estimations using Finite Element Analysis (FEA) are effective. However, producing a detailed finite element model would require an enormous number of elements and excessive calculation costs. To resolve this problem, we focused on periodic tube-fin structures, considering actual and designed fin shapes, and applied a homogenization method to the fins. We then determined their homogenization elastic stiffness and verified it by conducting compression experiments and analyses using partial models consisting of laminated tube-fin structures. If fins are homogenized, it is important that homogenization be based on the actual fin shape. We then produced a finite element model of a charge air cooler assembly by using the homogenization element, and conducted analyses which simulated a thermal fatigue test. Results indicated that qualitative identification of the area with the largest strain was possible. However, absolute strain values differed. We then made a detailed finite element model of the area with the largest strain and re-calculated the strain by supplying boundary displacements obtained from analysis of the assembly model and temperature distributions. Good agreement was obtained between experiment and analysis results. Using this method allows quantitative calculation of the thermal strain of heat exchangers.