Equimolar AlCoCrFeNi high-entropy alloy (HEA) often experiences serious oxidation degradation despite its superior mechanical properties at elevated temperatures. Herein, we reveal that minor Sc addition can enhance the oxidation resistance of AlCoCrFeNi HEA at 1100 °C, and the microstructure and oxidation properties for (AlCoCrFeNi)100−xScx HEAs (Sc-0, Sc-0.1, Sc-0.5 and Sc-1) are evaluated. Except for the original A2 + B2 phases, the Laves phase is found with increasing Sc addition. Moderate Sc addition is beneficial for interface adhesion by lowering the driving force for scale spallation and enhancing the interface toughness, and excessive Sc addition, however, results in serious internal oxidation due to the generation of Sc2O3 stringers as the high diffusivity paths for inward O ions. It is also proved that enhancing the interface toughness is more beneficial to improve the oxidation resistance compared to reducing scale growth rate. Our results can offer guidance for designing advanced alloys with excellent oxidation resistance.