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The rapid development of nanotechnology has generated numerous ideas for cancer treatment, and a wide variety of relevant nanoparticle platforms have been reported. Metal–organic frameworks (MOFs) have been widely investigated as an anti‐cancer drug delivery vehicle owing to their unique porous hybrid structure, biocompatibility, structural tunability, and multi‐functionality. MOF materials with catalytic activity, known as nanozymes, have applications in photodynamic and chemodynamic therapy. Nucleic acids have also attracted increasing research attention owing to their programmability, ease of synthesis, and versatility. A variety of functional DNAs and RNAs have been applied both therapeutically (gene‐targeting drugs for cancer treatment) and nontherapeutically (used as modified materials to enhance the therapeutic effects of other nanomedicines). The combined use of MOFs and functional nucleic acids have been extensively investigated and has been associated with excellent tumor‐suppressor activity in various treatment methods. In this review, we summarize the progress in the research and development of tumor therapy based on MOFs and nucleic acid delivery over recent years, focusing on the combinational use of different delivery and design strategies for MOF/therapeutic nucleic acid platforms. We further summarize the strategies for combining MOFs (universal carrier, functional carrier) and nucleic acids (therapeutic nucleic acids, nontherapeutic nucleic acids) and discuss the corresponding therapeutic effects in cancer treatment. This article is categorized under: Nanotechnology Approaches to Biology > Nanoscale Systems in Biology Therapeutic Approaches and Drug Discovery > Emerging Technologies

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