Objective:To investigate the clinical features of diffuse large B-cell lymphoma (DLBCL) of head and neck. Methods:A retrospective study was conducted among patients with DLBCL in the Department of otolaryngology and head and neck surgery of the Second Affiliated Hospital of Xi'an Jiaotong University from July 2011 to September 2021. The disease location, clinical manifestations, diagnosis, treatment and prognosis of DLBCL patients in head and neck were analyzed retrospectively. Results:Oropharynx(27 cases, including 25 cases in tonsil), neck(29 cases), nasopharynx and nasal cavity (7 cases)were included in 63 cases of DLBCL in head and neck. Pharyngalgia, pharyngeal foreign body sensation and dysphagia were the most common manifestations of oropharyngeal DLBCL, while nasal obstruction, runny nose and hyposmia were the initial manifestations of nasal and nasopharyngeal DLBCL.Under the NBI endoscopy, locally uplifted neoplasm with rough surface mucosa was observed in 34 cases DLBCL patients of oropharynx, nasopharynx and nasal cavity. Among them, 16 cases were covered with yellow-white and patchy pseudomembrane on the surface of the neoplasm, and 5 cases were detected with abnormal new vessels, including 3 cases of tonsils, 1 case of root of tongue, and 1 case of nasopharynx. Painless progressive lymphadenectasis was the common manifestation of DLBCL in head and neck, and the maximum diameter([21.3±6.7]mm) of neck lymph nodes in the same side of DLBCL was significantly larger than that in the opposite side([16.0±7.2]mm, P=0.009). Sixty-three cases of DLBCL in head and neck, including 27 cases of germinal center type(GCB), 33 cases of nongerminal center type(non-GCB), and 3 cases of non-specific DLBCL, were confirmed the diagnosis by needle biopsy(33 cases, 52.4%) and surgical resection(30 cases, 47.6%). The imaging features of DLBCL in head and neck were mostly showed as local soft tissue masses with uniform density and uneven enhancement, and the surrounding structures were often compressed and displaced. All the patients were treated with standard R-CHOP chemotherapy regimens, and overall survival was longer in normal LDH, and overall survival of the patients at low risk of IPI was longer than those at medium-high or high risk of IPI(PLDH=0.011, PIPI=0.022, P<0.05). Conclusion:DLBCL mainly occurs in oropharynx, especially the unilateral tonsil. When flake yellow-white pseudomembrane adhesion and abnormal neovessels on the surface of the mass are detected under endoscopy, and the ultrasound suggested multiple enlarged lymph nodes in the neck with large iplateral lymph nodes, the possibility of DLBCL should be considered. Surgical resection could be performed for diagnosis if necessary, and early diagnosis would have a better prognosis.