Perovskite light-emitting diodes (PeLEDs) provide new opportunities for cost-effective and large-area electroluminescent devices. It is of interest to use ZnO-based electron-transport layers (ETLs), which demonstrate superior performance in other solution-processed LEDs, in PeLEDs. However, the notorious deprotonation reaction between ZnO and perovskite casts doubt on the long-term stability of PeLEDs with ZnO-based ETLs. This Perspective presents an overview of the chemical reactions that may occur at the interfaces between perovskite and ZnO-based ETLs. We highlight that other interfacial reactions during the fabrication of PeLEDs, including the reactions between ZnO and the intermediate phase during perovskite crystallization and the amidation reactions catalyzed by ZnO, demonstrate critical utilities in the fabrication of high-efficiency and stable PeLEDs. Considering these recent advances, we propose future directions and prospects to design and control the interfacial reactions, aiming to fully exploit the potential of ZnO-based ETLs for realizing high-performance PeLEDs.