Microwave ablation (MWA) is a novel treatment modality that can lead to the death of tumor cells by heating the ions and polar molecules in the tissue through high-speed vibration and friction. However, the single hyperthermia is not sufficient to completely inhibit tumor growth. Herein, a thermodynamic cancer-therapeutic modality has been fabricated which could be able to overcome hypoxia's limitations in the tumor microenvironment. Using thermo-sensitive liposomes (TSL) and oxygen-independent radical generators (2,2'-azobis[2-(2-imidazolin-2-yl)propane]dihydrochloride, AIPH), a nano-drug delivery system denoted as ATSL is developed for efficient sequential cancer treatment. Under the microwave field, the temperature rise of local tissue could not only lead to the damage of tumor cells but also induce the release of AIPH encapsulated in ATSL to produce free radicals, eliciting tumor cell death. In addition, the ATSL developed here would avoid the side effects caused by the uncontrolled diffusion of AIPH to normal tissues. The ATSL have shown excellent therapeutic effects both in vitro and in vivo, suggesting its highly promising potential for clinic. This article is protected by copyright. All rights reserved.This article is protected by copyright. All rights reserved.