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The presence and effect of lattice distortion have become the most concerned issue of high-entropy alloys (HEAs) recently. To address this issue, TiZrNbTa (TZNT) HEAs were presented and an in-depth analysis concerning their microstructure, elemental diffusion and oxidation behavior was conducted. The results showed that during the high-temperature oxidation process at 800–1400 °C, the metastable homogeneous microstructure of TZNT HEAs segregated, then TiZr-rich and TaNb-rich regions with different lattice distortion degrees formed. Although O has stronger affinities with Ta and Nb, the oxygen atoms are more likely to diffuse in TiZr-rich region due to the dislocation pipe effect caused by severe lattice distortion. The inhomogeneous diffusion of oxygen atoms leads to inhomogeneous distribution of internal stress. The stress concentration and the structure transformation from BCC to brittle HCP jointly facilitate the cracks to form easier and grow in TiZr-rich region, finally resulting in a catastrophic pesting of TZNT HEAs at 800 °C. By contrast, the heterogeneity of oxygen atoms diffusion rate decreases as temperature increases. Therefore, the TZNT HEAs exhibited a parabolic oxidation behavior between 1000 and 1400 °C. The lattice distortion, whose degree is below the threshold for the generation of dislocation pipe effect, slows down the oxygen atoms diffusion rate. The findings of this work deepen the understanding on HEAs and can be utilized in tailoring the diffusion and oxidation behavior of high-performance HEAs via controlling lattice distortion. Image 1 • Effect of lattice distortion on diffusion behavior of high-entropy alloy is revealed. • Severe lattice distortion leads to a fast diffusion of O atoms via dislocation pipes. • Gentle lattice distortion hinders the diffusion of O compared with complete lattice. • Inhomogeneous diffusion in two distorted regions results in the pesting oxidation. [ABSTRACT FROM AUTHOR]