As one of the most commonly used chemotherapeutic agents in clinical practice, cisplatin is unable to selectively accumulate in tumor tissue due to its lack of targeting ability, leading to increased systemic toxicities. Additionally, the effectiveness of monotherapy is greatly limited. Therefore, the development of new cisplatin-based drug delivery systems is essential to improve the effectiveness of tumor treatment. In this study, an iron-based metal-organic framework (MOF) was synthesized to encapsulate cisplatin, and then coated with hyaluronic acid (HA) to create a MOF-based nanoplatform called MPt@HA NPs. This novel nanoplatform achieved the combination of chemodynamic therapy (CDT) with targeted chemotherapy for the treatment of lung cancer. The results showed that MPt@HA NPs have stronger cytotoxicity compared to conventional doses of cisplatin due to the generation of reactive oxygen species (ROS) through the Fenton reaction and DNA damage caused by cisplatin. Therefore, MPt@HA NPs effectively inhibit the tumor growth and prolong the median survival of tumor-bearing mice. Therefore, the MOF-based nanoplatform MPt@HA NPs may present a new option for multi-modal therapy of solid tumors.