Abstract This study investigated the effect of the microstructure refinement on the oxidation resistance of the Nb-6Mo-20Si-3Cr silicide-based alloy based on how the oxidation behavior of the alloy is severely affected by its microstructure size. Alloy powders were fabricated by a hydrogenation-dehydrogenation method, and were consolidated by a spark plasma sintering process. The sample, having a refined microstructure, could be fabricated by adopting a powder metallurgy method, and its microstructure is much finer than that of the sample fabricated by arc casting. To compare the oxidation resistance, the cast ingot and the sintered compact were oxidized at 1200 °C at various durations in an air atmosphere. The oxidation behavior of both followed the parabolic rate law. Based on the oxidation results, the parabolic rate constant of the cast ingot was 5.93 × 10−7 g2cm−4s−1, while, in the SPS compact, it was decreased to 2.31 × 10−7 g2cm−4s−1. By the microstructure and oxidation behavior results, this study confirms that the oxidation resistance of the Nb-6Mo-20Si-3Cr alloy could be improved by microstructure refinement.