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• G-CSF to WBRT + ICIs as a first-line treatment prolonged OS of NSCLC brain metastases. • G-CSF may improve neurological symptoms in patients undergoing WBRT. • G-CSF effectively reduced the incidence of neutropenia after ICIs, further preventing severe infections. To evaluate the therapeutic advantage of G-CSF to whole brain radiotherapy (WBRT) in combination with immunotherapy as a first-line treatment for non-small cell lung cancer (NSCLC) brain metastases (BMs). In this retrospective study, 117 patients (37 in G-CSF group and 80 in no G-CSF group) who underwent first-line WBRT combined with immunotherapy were enrolled. Their survival, intracranial response, BM-related symptoms and toxicity were evaluated. The overall survival (OS) of patients in G-CSF group was significantly improved compared to patients no G-CSF group (median time: 14.8 vs 10.2 months; HR: 0.61, 95 % CI: 0.38–0.97, p = 0.035). However, there were no significant differences in intracranial responses between the two groups (p > 0.05). The G-CSF group exhibited a significantly higher rate of relief from BM-related symptoms compared to the no G-CSF group (91.7 % vs 59.5 %, p = 0.037). Cox proportional hazards regression analyses indicated that after-treatment ALC > 0.9 × 10^9/L (HR 0.57, 95 % CI 0.32–0.99, p = 0.046) and Hb > 110 g/dL (HR 0.41, 95 % CI 0.24–0.71, p = 0.001) were significant potential factors associated with extended OS. The addition of G-CSF was well tolerated and effectively reduced the incidence of neutropenia (0 % vs 5.0 %, p = 0.17). Integrating G-CSF with WBRT and immunotherapy as a first-line treatment for NSCLC-BMs has exhibited significant efficacy and favorable tolerability. [ABSTRACT FROM AUTHOR]