Hypoxia is a common phenomenon in the majority of solid tumours, thereby contributing to progression, angiogenesis, invasion, and metastasis of tumours. The authors synthesised a hypoxia-responsive (HR) magnetic iron oxide nanoparticles (IONPs) as drug delivery system by incorporating a hypoxia moiety (azobenzene) between IONPs and drug. The obtained drug delivery system showed sustained release under normoxic conditions, while a controlled release was observed under hypoxic condition due to the cleavage of azobenzene. More than 80% of the drug was released in 4 h after hypoxic treatment, leading to a high cytotoxicity. Thus, this HR magnetic drug delivery system had the potential for future applications in the treatment of hypoxic tumours and other hypoxia-related diseases.