Taken together, we hypothesized that the APE1/IL‐6/STAT3 signalling might have a role to confer in the drug resistance of NSCLC to Erlotinib, and that the construction of CSC‐derived EVs targeting this signalling may serve as a promising approach to reverse the Erlotinib resistance in NSCLC. Here, APEX1 is linked to non-small cell lung carcinoma.