The identification of genetic modifications in the epidermal growth factor receptor (EGFR) and anaplastic lymphoma kinase (ALK) in non-small cell lung cancers has resulted in notable shifts in the approach to treatment, and has shown considerable improvements in patient survival rates. Research indicates that the fusion mutation of the ALK gene is one of the mechanisms responsible for resistance to EGFR-tyrosine kinase inhibitors (TKI). In this case report, we present the case of a 64-year-old female patient with advanced lung adenocarcinoma, who initially harbored an EGFR mutation but subsequently developed ALK fusion following treatment with EGFR-TKIs. Through sequential using EGFR-TKIs or ALK-TKIs, a long survival was achieved, hoping to guide the choosing of target therapy drugs for patients with ALK fusion-mediated EGFR-TKIs resistance.