Abstract: Small interfering RNA (siRNA)-mediated RNA interference (RNAi) technology has been extensively studied, but its clinical applications still face challenges, including poor pharmacokinetic properties, susceptibility to enzymatic degradation, low cell uptake rate, and non-specific gene silencing. Developing siRNA delivery vehicles with high silencing efficiency, good biocompatibility, and facile functionalization is crucial for advancing siRNA therapies toward clinical translation. This article reviews the latest research progress on metal-organic frameworks (MOFs) as highly promising non-viral carriers for siRNA delivery, aiming to provide insights and references for the design of efficient siRNA delivery platforms.