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[Purpose] Chemotherapy and epidermal growth factor receptor tyrosine kinase inhibitor(EGFR-TKIs) treatments remain under dispute for patients with brain metastases from non-small cell lung cancer(NSCLC).[Methods] We retrospectively studied the outcomes of solely localized treatments or localized treatments in combination with chemotherapy and/or EGFR-TKIs medications for 210 NSCLC patients with brain metastases.The effects of treatment modality, Karnofsky performance status(KPS), age, primary tumor histology, number of brain metastases and other factors on survival were analyzed and the robustness of two prognostic indices (the RPA and GPA models) were evaluated.[Results] The median survival time (MST) for patients with systemic medication and localized treatments was higher than that with localized treatments alone (11.0 vs 3.0 months,P=0.000).Within the systemic medication group,the MST was significantly higher for EGFR-TKI than that for chemotherapy treatments (12.0 vs 9.0 months, P=0.002).The MST of patients with mutated EGFR gene was 20 months vs 8 months for patients with the EGFR wild type gene in the EGFR-TKI group.The MST with pemetrexed medication was significantly higher than that with other chemotherapies (13.0 vs 7.0 months,P=0.006).In a multivariate analysis,prognosis was significantly correlated with treatment modality (P=0.000),KPS (P=0.000), number of brain metastases (P=0.001) and tumor histological type (P=0.007).In the Graded Prognostic Assessment (GPA) model, the survival curves of subgroups showed clear separations.[Conclusions] NSCLC patients with brain metastases had a longer survival benefit from chemotherapies, especially pemetrexed and/or TKIs along with localized treatments and the GPA index is a robust model for prognostic evaluation.