Advanced non-small-cell lung cancer (NSCLC) patients with EGFR exon 19 deletion often get benefits from the treatment of tyrosine kinase inhibitors (TKI). In the same way, the NSCLC patients with mesenchymal-to-epithelial transition (MET) amplification get benefits from crizotinib. The treatment becomes extremely difficult for the patients with both EGFR exon 19 deletion and MET amplification, after failure of first-line TKI. An advanced NSCLC patient with EGFR exon 19 deletion was treated with TKI. However, the disease recurred after four months. MET amplification was found after biopsy again. The patient was treated with the combination of crizotinib, while the disease recurred after eight months. The patient was treated by pembrolizumab and pemetrexed + carboplatin chemotherapy as salvage therapy. The therapeutic effect has been remarkable up to present. In conclusion, immunotherapy combined with chemotherapy could be a promising therapy for the NSCLC patients with both EGFR exon 19 deletion and MET amplification after the failure of first-line TKI treatment. Thus, further insights into the variant genes contribute to NSCLC treatment.