to their noninvasive and specific treatment modality from selective irradiation. [1b] However, external energy, such as light, ionizing radiation or ultrasound, is required in these therapies, which obstructs their further development due to the limited penetration depth of the laser, safety concerns of radiation, therapeutic resistance and spatio-temporal constraints of some specific equipments. In-depth exploiting the differences between the tumor microenvironment (TME) and normal organs provides an alternative way that without specific devices. Take full advantage of the TME, endogenousstimuli-mediated therapy is a novel concept in tumor treatment.The TME, mainly composed of tumor cells, vessels, lymphatic vessels, immune cells, fibroblasts, and extracellular matrix (ECM), [4] which provides a suitable environment for survival, division, angiogenesis, and metastasis of tumor cells. During the growth of tumor tissue, some regions are hypoxic [5] due to abnormal vascularization and inferior blood accommodation. [6] Normal cells can decompose glucose into pyruvate through glycolysis in the cytoplasm under normoxic conditions and the generated pyruvate is transported to the mitochondria and further decomposed into carbon dioxide, [7] which is known as tricarboxylic acid cycle (TCA). In hypoxic tumor tissues, the TCA pathway is restricted due to the insufficiency of oxygen supply. Instead, pyruvate is reduced to lactic acid to produce energy with much lower efficiency. This process on the one hand increases the consumption of glucose and pyruvate, and on the other hand increases acidity of the extracellular TME (pH value: 6.5-6.8) due to the secreted lactic acid. [8] Another noteworthy property of the TME is the increased level of reactive oxygen species (ROS). [9] The term ROS mainly includes hydrogen peroxide (H 2 O 2 ), singlet oxygen ( 1 O 2 ), hydroxyl radical (•OH), superoxide (•O 2 − ), ozone, lipid peroxides, hypochlorous acid, which often determines many biological responses and metabolic processes within the tumor [10] directly and/or indirectly. [11] Increased expression of ROS-scavenging enzymes and antioxidant molecules could balance the high levels of ROS, which may contribute to the accommodative response of tumor cells to many therapies. [12] For example, glutathione (GSH) plays a vital role in the protection of cells against lectrophilic and oxidative stress as it is engaged in the metabolism and detoxification process of many cytotoxic and carcinogenic species with the oxidation of GSH to its oxidized Though numerous external-stimuli-triggered tumor therapies, including phototherapy, radiotherapy, and sonodynamic therapy have made great progress in cancer therapy, the low penetration depth of the laser, safety concerns of radiation, the therapeutic resistance, and the spatio-temporal constraints of the specific equipment restrict their convenient clinical applications. What is more, the inherent physiological barriers of the tumor microenvironment (TME), including hypoxia, heterogeneity, and...