e18532 Background: Previous studies have been reported that the frequency of NTRK ( NTRK1 NTRK2 NTRK3) fusion varies from up to 1% in solid or hematological cancers but more common in rare tumor types, such as mammary-analog secretory carcinoma of the salivary gland (more than 90%), thyroid cancer (up to 25%) and gastrointestinal stromal tumour (up to 25%). The specific TRK inhibitor Larotrectinib and multiple TRK inhibitor Entrectinib have been approved by FDA for advanced solid tumors. Here we report the incidence of NTRK alteration in Chinsese Head and Neck cancer and a patient harboring ETV6- NTRK3 fusion acquired durable clinical response to multiple TRK inhibitor Crizotinib. Methods: We retrospectively analyzed the genetic aberrations in 127 patients of Chinese Head and neck cancer. All the patients were detected by hybridization capture-based NGS 1021-gene panel (including NTRK1 NTRK2 NTRK3) sequencing with tumor tissue and peripheral blood control samples. A parotid cancer patient with lung metastasis harboring ETV6-NTRK3 fusion underwent Crizotinib treatment after disease progressed with chemotherapy. Results: A parotid cancer patient with lung metastasis harboring ETV6-NTRK3 fusion was diagnosed on Mar. 2016. Five months after first-line chemotherapy, the disease progressed. Crizotinib was administered from Aug. 2017 to Sep. 2019 with regular CT examination. The latest CT on Sep. 2019 showed mixed response, some of the lesions shrunk but one of them enlarged. Then the patient received third line chemotherapy. In brief, the patient reached a progression-free survival (PFS) of 2 years. Then we reviewed 127 cases of Head and Neck cancer in our database, the most common histology type was HNSCC (87.4%), the incidence of NTRK genetic aberrations was 7.9% (10/127) including NTRK fusion (n = 4, 3.1%) and NTRK mutation (n = 6, 4.7%). The most common fusion was ETV6-NTRK3 (n = 3, 2.4%). Conclusions: In conclusion, we reported the incidence of NTRK genetic aberrations in Chinese Head and Neck cancer and an ETV6-NTRK3 fusion patient reached long-term response (2 years) with Crizotinib, indicating alternative therapy insights to Head and Neck Cancer patients.