Silencing CASC8 can increase the sensitivity of NSCLC cells to osimertinib via FOXM1. These findings not only provide new insights for the clinical application of CASC8 polymorphisms in predicting cancer risk and chemotherapy response but also provide new directions for exploring the effect of CASC8 SNPs on chemotherapy. Here, CASC8 is linked to non-small cell lung carcinoma.