In this study, our results provide the first evidence that the EIF2B4-SFN fusion and increased SFN expression, which activate the PI3K/Akt pathway, are associated with chemotherapy tolerance and poor prognosis in NSCLC patients, suggesting that SFN has potential prognostic value as a molecular marker to identify patients who can possibility benefit from combined treatment. Here, EIF2B4 is linked to non-small cell lung carcinoma.