〔Abstract〕 Objective To explore the correlation between epidermal growth factor receptor(EGFR) mutation and brain metastasis in lung adenocarcinoma. Methods Comparisons of brain metastasis between lung adenocarcinoma patients with EGFR exon 19 deletion(19 Del) and a single point mutation of L858R in exon 21(21 L858R) at initial diagnosis and after EGFR-TKIs targeted therapy were analyzed. The CCK-8 assay was used to detect and calculate the semi-inhibitory concentration(IC50) of gefitinib against EGFR-mutated lung adenoma cell lines PC9 and H3255. Results Of the 410 patients with lung adenocarcinoma, a total of 153(37.3%) cases had brain metastasis. Age, lymph node metastasis and 21 L858R mutation were high-risk factors for brain metastasis of lung adenocarcinoma. Among newly diagnosed 48 EGFR-mutated lung adenocarcinoma patients with brain metastasis, the number of 19 Del and 21 L858R were 14 and 34, respectively(P=0.006). There were 17 patients with 19 Del and 20 patients with 21 L858R were observed to complicated by brain metastasis after receiving EGFR-TKIs targeted therapy. The median time of brain metastasis after EGFR-TKIs treatment were 15 months(8.50, 25.00) and 7 months(4.25, 12.25), respectively(P=0.013). The IC50of PC9 and H3255 to gefitinib were(0.037±0.008)and(0.150±0.040)μmol/L, respectively(P=0.007). Conclusion Age younger than or equal to 60 years, lymph node N2-3 stage, and EGFR 21 L858R mutation are high-risk factors for brain metastases in patients with lung adenocarcinoma, and the latter still has a shorter time to brain metastases than 19 Del mutations after treatment with EGFR-TKIs, which may be related to drug sensitivity.