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Objective: The aim of this study was to define the maximum-tolerated dose (MTD) and observe the toxicity of escalating topotecan combined whole brain radiotherapy for brain metastasis in lung cancer. Methods: Patients with brain metastasis of lung cancer received conventional fractionation radiotherapy, with 5 daily fractions of 2 Gy per week, the total radiation dose was 40 Gy, while the larger lesions were boosted to 50-60 Gy. The initial dose of topotecan was 1.0 mg/m2. Escalation dose was 0.25 mg/m2. Every cohort contained at least 3 patients.If no dose-limiting toxicity (DLT) was observed,the next dose level was opened for entry. These courses were repeated until DLT appeared. MTD was declared as one dose level below which DLT appeared. Results: Eighteen patients were recruited. Two cases of grade 3 leucopenia/neutropenia was observed as DLT at the level of topotecan 2.0 mg/m2. MTD of topotecan was defined as 1.75 mg/m2.The major side effects were leucopenia/neutropenia, nausea and vomiting. Conclusion: Topotecan combined with whole brain radiotherapy for brain metastasis in lung cancer is well tolerated. Maximum-tolerated dose of topotecan is 1.75 mg/m2, once a week of a total of four.