With great power comes great challenges. For nuclear fusion, the holy grail of energy, taming the flame of a miniature star in a solid container remains one of the most fundamental challenges. A tungsten armour for the solid container marks a temporary triumph—a solution adopted by the world’s largest fusion experiment, ITER—but may be insufficient for future challenges. High-entropy alloys (HEAs), which are characteristic of a massive compositional space, may bring new solutions. Here, we explore their potential as plasma-facing materials (PFMs) with a prototype W57Ta21V11Ti8Cr3 HEA that was designed by exploiting the natural-mixing tendency among low-activation refractory elements. Revealed by x-ray diffraction analysis and energy-dispersive x-ray spectroscopy, it predominantly consists of a single bcc-phase but with V, Ti, and Cr segregation to grain boundaries and at precipitates. Its yield strength improves ∼60% at room temperature and oxidation rate reduces ∼6 times at 1273 K, compared with conventionally used W. The Ti–V–Cr rich segregations and the formed CrTaO4 compound contribute to the improved oxidation resistance. However, the Ti–V–Cr rich segregations, along with the decreasing valence-electron concentration of the matrix by the addition of Ta, V and Ti elements, considerably increase the deuterium retention of the W57Ta21V11Ti8Cr3 HEA to ∼675 multiples of recrystallized W. Moreover, its thermal conductivity decreases, being ∼40% of W at 973 K. However, the maximum tolerable steady-state heat load is still ∼84% of W because of its exceedingly high yield strength at elevated temperatures. Overall, despite being preliminary, we expect HEAs to play an important role in the development of advanced PFMs, for their disadvantages are likely to be compensated by their advantages or be overcome by composition optimization.