In fact, brain metastases are the most common intracranial tumors, and 8%-10% of tumor patients have brain metastases with neurological symptoms, and brain metastases of lung cancer patients account for 40%-70% of intracranial metastases, so the treatment of non-small cell lung cancer brain metastases touches the “nerves” of clinical oncologists. How to make better use of these treatment methods to treat brain metastases, prolong patients’ survival and protect the function of central nervous system is a major issue that cannot be ignored. The incidence of brain metastases from lung cancer accounts for 40%-60% of brain metastases from all solid tumors, and its biological behavior is highly invasive, with poor prognosis and often accompanied by the decline of patients’ quality of life. At present, the treatment for brain metastases is limited, and surgery or stereotactic radiotherapy is mostly used for isolated lesions, while for multiple lesions, whole brain radiotherapy is the main treatment. The natural barrier of the blood-brain barrier has kept drug therapy in a relatively secondary position. Theoretically, after brain metastasis of lung cancer occurs, the blood-brain barrier will be partially destroyed, which is conducive to the penetration of drugs. However, in clinical practice, the efficacy of both drugs sensitive to extracerebral lesions and chemotherapeutic drugs that can completely cross the blood-brain barrier, such as nitrosoureas and VM-26, is not satisfactory. The emergence of new drugs such as temozolomide, pemetrexed and small molecule tyrosine kinase inhibitors in recent years has undoubtedly brought a ray of hope for patients with brain metastases. Temozolomide is a novel imidazotetrazine alkylating agent with complete oral absorption, high bioavailability, and ability to cross the blood-brain barrier. Its efficacy in glioma has been demonstrated, and its efficacy in brain metastases from solid tumors such as lung cancer has also been shown. An Italian phase II study evaluated the efficacy of standard TMZ monotherapy (150-200 mg/m2/d, d1-5, repeated every 28 days) as salvage therapy for brain metastases from non-small cell lung cancer (NSCLC). The study enrolled 30 patients with NSCLC and showed an objective remission rate (ORR) of 10% for brain metastases and overall time to disease progression (TTP) and overall survival (OS) of 3.6 months and 6 months, respectively, with patients achieving objective remission achieving TTP and OS of 11-19 months and 14-24 months, respectively. Another phase II study used TMZ at a low daily dose (75 mg/m2/d, d1-21, repeated every 28 days) to treat relapsed refractory NSCLC, in which 39% of patients with combined brain metastases had a disease control rate (DCR) of 16.2% and TTP and OS of 2.4 and 3.3 months, respectively. Both clinical studies showed the efficacy of TMZ as a second-line or higher treatment for brain metastases from NSCLC, which warrants a phase III clinical study. TMZ combined with radiotherapy for brain metastases has also shown good efficacy. In a phase II clinical study in France, 50 patients with NSCLC brain metastases were treated with TMZ combined with cisplatin chemotherapy in sequential whole brain radiotherapy, and the results showed an ORR of 16%, TTP and OS of 2.3 months and 5 months, respectively. Two other phase II clinical studies on concurrent TMZ radiotherapy showed ORR of 45%-57.6% and OS of 12-13 months. These studies suggest that concurrent radiotherapy may be superior to sequential radiotherapy or single chemotherapy. In addition, TMZ may also have a role in the prevention of brain metastases. One study showed that only 8% (3/37 cases) of patients treated with TMZ in combination with topotecan for NSCLC eventually developed brain metastases, much lower than the 50% incidence of brain metastases reported in other literature, suggesting that TMZ may have a potential role in preventing brain metastases. the role shown for TMZ in the treatment of brain metastases from lung cancer warrants further clinical trials. Based on the performance of TMZ in brain tumors and various brain metastases, the 2009 edition of the NCCN guidelines recommends it as one of the chemotherapy options for brain tumors.