Thermal fatigue failure is one of the main factors affecting the service life of hot work die steel. Achieving excellent thermal fatigue resistance for hot working die steels can benefit the industry economically. In this work, (TiC + TiB2)/Al master alloys were used to add TiC–TiB2 nanoparticles into high-Cr die steels, which achieves microstructure manipulation and obtains excellent thermal fatigue resistance and strength-plastic combination. The results showed that after being manipulated by 0.02 wt% TiC–TiB2 nanoparticles, the surface oxidation zone of the high-Cr die steel after different thermal fatigue cycles is reduced than high-Cr die steel without manipulation. TiC–TiB2 nanoparticles effectively refined the heat-treated microstructure of high-Cr die steel, promoting the Cr element and alloy carbides being more uniformly distributed in the matrix, which prevents the occurrence of oxidative pitting and conducive to the formation of a dense and uniform Cr2O3 oxide layer, and further preventing the initiation of thermal fatigue cracks. Moreover, these finer and more uniformly distributed precipitates in TiC–TiB2 nanoparticles manipulated high-Cr die steels will promote stress dispersion and hinder thermal fatigue crack propagation. This work provides a promising avenue for the design of low-cost, high-performance, and long-life die steels for industrial applications. •The microstructure has been manipulated with traces TiC–TiB2.•Thermal fatigue cracks initiation are closely correlated to surface oxidative erosion.•Nanoparticle-reinforced steels have better thermal fatigue resistance.