Photocatalysis is a promising technology to resolve energy and environmental issues, where the design of high-efficiency photocatalysts is the central task. As an emerging family of photocatalysts, semiconducting metal-organic frameworks (MOFs) with remarkable features have demonstrated great potential in various photocatalytic fields. Compared to MOF-based photocatalysts with a single component, construction of S-scheme heterojunctions can render MOFs with enhanced charge separation, redox capacity and solar energy utilization, and thus improved photocatalytic performance. Herein, an overview of the recent advances in the design of MOF-based S-scheme heterojunctions for photocatalytic applications is provided. The basic principle of S-scheme heterojunctions is introduced. Then, three types of MOF-based S-scheme heterojunctions with different compositions are systematically summarized including MOF/non-MOF, MOF-on-MOF and MOF-derived heterojunctions. Afterwards, the enhanced performances of MOF-based S-scheme heterojunctions in hydrogen production, CO2 reduction, C-H functionalization, H2O2 production and wastewater treatment are highlighted. Lastly, the current challenges and future prospects regarding the design and applications of MOF-based S-scheme heterojunctions are discussed to inspire the further development of this emerging field.