Hybrid catalysis provides an effective pathway to improve the catalytic efficiency and simplify the synthesis operation, but multiple catalytic sites are required. Catalysts with multiple functions based on/derived from metal-organic frameworks (MOFs) have received growing attention in organic synthesis due to their wide variety and outstanding designability. This review provides an overview of significant advances in the field of organic reactions by MOF-based hybrid catalysts with emphasis on multiple catalytic sites and their synergies, including inherent sites on host frameworks, sites of MOF composites and metal sites in/on MOF-derived hybrid catalysts.