Background: Non-small cell lung cancer with brain metastasis (NSCLCBM) is normally observed in advanced-stage patients. Bevacizumab has shown to improve survival in the first-line treatment of metastatic brain NSCLC when added as a bolus plus irinotecan. However, a better understanding of the molecular mechanism is required to further drive progress in this field.Methods: A total of 155 patients were selected, including 42.10% with Kirsten rat sarcoma viral oncogene homolog (Kras)-mutant tumors. Of the 155 patients, 62.04% had developed brain metastasis (BM). Seven functional single-nucleotide polymorphisms (SNPs) in the Kras gene were extracted from the HapMap SNP database and were used for genotyping. The haplologit command in Statistical Software for Data Science (STATA) was used to model the association between haplotypes and case status. A Cox analysis was used to evaluate the prognostic value of the SNPs.Results: Among the patients treated with combination regimens, recurrence after local treatment was more frequent in those with two types of Kras mutations (odds ratio [OR] = 2.033 [0.5015-4.2552], p = 0.009). Among the patients with untreated BM, overall survival was shorter than that of patients with Kras mutations according to univariate analysis (OR = 5.130 [1.240-41.012], p = 0.033).Conclusions: Kras mutations have a predictive role for BM recurrence and outcome in patients with NSCLC treated with bevacizumab combination regimens.