Non-small cell lung cancer (NSCLC) patients with anaplastic lymphoma kinase (ALK) rearrangement benefit from treatment with ALK inhibitors. Therefore, the identification of druggable ALK fusions is necessary for NSCLC treatment. More than 90 fusion partners of ALK have been reported in NSCLC patients, but the striatin gene (STRN)-ALK fusion has rarely been reported. Moreover, the response of STRN-ALK fusion patients treated with ALK inhibitors remains to be explored. A 64-year-old Chinese male with no history of smoking or alcohol consumption was diagnosed as stage IVB lung adenocarcinoma (LADC) (cT4N3M1c) in October 2018. Next-generation sequencing (NGS) targeting 425 cancer-related genes was performed on the plasma and supernatant of pleural effusion samples and revealed an STRN-ALK fusion. The patient received alectinib (600 mg, twice daily) as the first-line treatment with an excellent response exceeding 19 months. This is the first report of a NSCLC patient harboring an STRN-ALK fusion and exhibiting an excellent response to alectinib treatment. This case provides valuable information for therapeutic decision-making of patients with STRN-ALK fusions. Furthermore, this case also highlighted the advantage of performing targeted NGS on circulating tumor DNA for the identification and analysis of rare, druggable genomic alterations.