Epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) are the standard therapy for patients with advanced non-small-cell lung cancer (NSCLC) harbouring common EGFR mutations. However, about 10% of EGFR mutations are uncommon mutations and their response to EGFR-TKIs remains unclear. The present case reports a 75-year, female patient with advanced NSCLC, presenting with a new subtype of EGFR exon 19 insertion mutation (IPVAIL insertion), who showed obvious symptom improvement after EGFR-TKIs treatment but a relatively short time of progression-free survival (PFS) and succumbed to tumor 133 days (4.4 months) after diagnosis. In conclusion, patients harbouring new subtype of EGFR exon 19 insertion mutations, IPVAIL insertion may have a poor prognosis. Further experiences are required to characterise these uncommon mutations.