Abstract: The thermal management technique of multi-layer Cr4+:YAG medium was presented for mitigating the deleterious impact of thermal effects in a cryogenic helium gas cooled Yb:YAG multislab amplifier with Cr4+:YAG interlayers operating at a high repetition rate, by means of optimizing the architectures of Cr4+:YAG interlayers and claddings in the laser slabs. The distributions of temperature, stress, depolarization losses and optical path difference in four amplifier architectures with different Cr4+:YAG parameters were numerically calculated by a three-dimensional finite element analysis and the Jones matrices method. Based on these results of the propsed modelling, it was showed that the properly designed two-layer and three-layer Cr4+:YAG could decrease the heat deposition of the Cr4+:YAG around the gain media, and hence result in a very small transverse temperature gradient (1.5 K) in the first slab. When the laser beam traveled through the whole amplifier, the average thermal-stress induced depolarization losses and optical path difference for the laser amplifier head were reduced to 0.5% and 0.8, respectively. Furthermore, the negative impact of thermal effects on the output beam quality can be vanished by properly designing the number, widths, and absorption coefficients of the multi-layer Cr4+:YAG medium, which are beneficial for the engineering/design of the next generation of high energy, high power lasers.