To evaluate the structural failure risk of the regenerative cooling thrust chamber cylinder segment, a Finite Element Method (FEM) based on experimental data was developed. The method-ology was validated and utilized to reveal the thermal response and the nonlinear deformation behavior of the cylinder segment phase by phase. The conclusions of the research are as follows:The 2D heat flux distribution caused by the injector determines the uneven temperature distribution on the gas-side wall and leads to the temperature disparity between various cooling channels;The reason for the accumulation of residual strain is that the tensile strain generated in the post-cooling phase is greater than the compressive strain produced in the hot run phase;Through the single-cycle simulation, two potential failure locations with conspicuous deformations were found, but it is dif-ficult to determine which point is more dangerous. However, the multi-cycle thermo-structural anal-ysis gives the evolution of the stress-strain curve and gradually discloses that the low-temperature cer of a particular channel is the most likely location to fail, rather than the maximum residual strain point of the gas-side wall. The damage analysis for dangerous point indicates that the quasi-static damage accounts for the majority of the total damage and is the main factor limiting the ser-vice life.