The tuyere sleeve plays a crucial role in blast furnaces, enduring a harsh working environment that frequently leads to substantial damage. One approach to extend the service life of tuyere sleeve is to prepare a Ni-based alloy protective layer on its surface. However, there is a lack of experimental information concerning the failure of these protective coatings after real-world use. Therefore, in this study, the failure of a blast furnace tuyere sleeve with protective layer was investigated. Characterizations were performed on both the “original” and failed protective layers, as well as the scale layer. The “original” protective layer exhibits two main issues: excessive copper dilution (>40%) and significant Ni-Cr enrichment at the interface, which may be attributed to inadequate preparation techniques. The failed protective layer surface is covered with molten slag and iron, and there is a crack running almost completely through the coating. Both oxidation reaction and sulfur corrosion are important factors contributing to the accelerated failure of the coating. Moreover, it is suggested that the compositional inhomogeneity of the protective layer of the tuyere sleeve leads to local stress concentration within the coating, which is an internal cause for thermal fatigue crack formation. Additionally, it can be inferred that the molten slag and iron falling onto the protective layer surface under abnormal furnace conditions not only accelerates crack initiation and propagation but also directly melts the coating material or causes interface reactions, leading to the failure of the protective layer.