In summary, the study has established the efficacy and related mechanisms of the combination of Rapa and Osi in alleviating NSCLC and laied the groundwork for future research on overcoming Osi-resistant NSCLC patients with Rapa, but additional studies should be warranted to further elucidate the therapeutic mechanisms of the Rapa-Osi combination in treating NSCLC. Here, TRERF1 is linked to non-small cell lung carcinoma.