Taken together, our results show that mutant EGFR‐driven NSCLC cells made resistant to osimertinib have increased CSPG4 expression and reducing its expression by transient siRNA transfection had a modest, but still significant, effect on the cell viability, illustrating a possible role for CSPG4 in osimertinib refractoriness at least in a subset of mutant EGFR‐driven NSCLC. Here, EGFR is linked to non-small cell lung carcinoma.