Abstract: Objective This study aimed to investigate the relationship between EGFR gene mutation and the efficacy of blinatumomab in the treatment of adult relapsed or refractory acute lymphoblastic leukemia (R/R ALL). Methods A retrospective analysis was performed on the medical records of 104 adult patients with R/R ALL who received blinatumomab treatment in Zhujiang Hospital of Southern Medical University from August 2020 to July 2023. The EGFR gene mutation status of the patients was analyzed. The hierarchical regression model, multivariate logistic regression model, receiver operating characteristic (ROC) curve and survival curve were used to analyze the influence of EGFR gene mutation on the therapeutic efficacy and prognosis. Results The mutation rate of the EGFR gene was 35.58%, with the mutation effect being mainly missense mutations and the mutation pattern being mainly point mutations among the positive samples. There were statistically significant differences in EGFR expression level, therapeutic effects and prognosis among patients with different EGFR gene mutations (P＜0.05), and in EGFR expression level and EGFR gene mutation among patients with different prognoses (P＜0.05). EGFR gene mutation was an independent risk factor for poor prognosis in adult patients with R/R ALL (P＜0.05). With the incorporation of EGFR gene mutations, the diagnostic efficacy of the prediction model for poor prognosis and therapeutic effect increased. The 1-year overall survival (OS) and event-free survival (EFS) of patients in the EGFR-positive group were significantly lower than those of patients in the EGFR-negative group (P＜0.05). Conclusion EGFR gene mutation has some influence on the efficacy of blinatumomab in the treatment of adult patients with R/R ALL. It is an independent risk factor affecting the poor prognosis of adult patients with R/R ALL, with a significant impact on 1-year OS and EFS.