The design and development of multifunctional nano-drug delivery systems (NDDSs) is a solution that is expected to solve some intractable problems in traditional cancer treatment. In particular, metal-organic frameworks (MOFs) are novel hybrid porous nanomaterials which are constructed by the coordination of metal cations or clusters and organic bridging ligands. Benefiting from their intrinsic superior properties, MOFs have captivated intensive attentions in drug release and cancer theranostic. Based on what has been achieved about MOF-based DDSs in recent years, this review introduces different stimuli-responsive mechanisms of them and their applications in cancer diagnosis and treatment systematically. Moreover, the existing challenges and future opportunities in this field are summarized. By realizing industrial production and paying attention to biosafety, their clinical applications will be enriched.