Tumor hypoxia is intimately associated with gliomas, which represents a significant threat to human health and are resistant to the first-line chemotherapeutic drug temozolomide (TMZ) due to hypoxia. In this work, to overcome TMZ resistance in orthotopic gliomas, aptamer-functionalized liposomes are manufactured to encapsulate TMZ and photothermal agent IR780, and can cross the blood-brain barrier and actively target gliomas. It is possible to employ liposomes for both fluorescence and photoacoustic imaging simultaneously due to their stability and excellent photothermal conversion capabilities. This chemo/photothermal synergistic therapeutic effect of liposomes on gliomas is demonstrated by their abilities to target orthotopic gliomas, alleviate tumor hypoxia and consequently reverse resistance of glioma cells to TMZ, thereby extending the survival time of tumor-bearing mice, making the nanoplatforms and their synergistic chemo/photothermal therapy as a potential clinical treatment for gliomas.