The prognostic value of the systemic immune-inflammation index (SII) has been shown in various types of cancers. We aimed to evaluate the predictive values in brain metastases from lung adenocarcinoma with status of EGFR mutations. We, retrospectively, examined 310 patients with brain metastases from lung adenocarcinoma with status of EGFR mutations. SII was calculated using P * N/L, where P, N, and L, respectively refer to peripheral blood lymphocyte, neutrophil, and platelet counts. The cut-off value of SII was assessed by area under the curve (AUC). The log-rank test and Cox proportional hazard model were used to confirm the impact of SII and other variables on survival. The SII value ≤ 1218.81 was associated with prolonged survival in patients with brain metastases from lung adenocarcinoma in both variable and multivariable analysis In patients with EGFR mutations, the SII had statistical effect on OS only in invariable test. While, for patients with wild-type EGFR, SII achieved statistically significant differences both in variable and multivariable analyses. SII is an independent prognostic factor in brain metastases from lung adenocarcinoma. SII may have varying prognostic effects on patients with and without EGFR mutations and is a promising variable for the future prognostic systems.