Objective To explore the clinical features, diagnosis and treatment of hereditary hemorrhagic telangiectasia (HHT)，it will provide help for the early diagnosis of HHT in clinical work. Methods It was retrospectively analyzed for the clinical data and family status of a patient admitted to the Departmant of Otorhinolaryngology Head and Neck Surgery of the Affiliated Hospital of Guangdong Medical University due to “recurrent nasal bleeding for 6 years”. The whole exome sequencing (WES) was used to screen suspected pathogenic genes in probands, and Sanger sequencing was used to verify the pedigree of the probands and their family members. Results Both the proband and his father had recurrent epistaxis and mucous telangiectasia. The younger brother of the proband had a history of cerebrovascular malformation. WES revealed that the proband carried a heterozygous mutation of ENG gene C.1361T>C(p.Leu454Pro), while Sanger sequencing showed that his father carried the same mutation. Conclusion The heterozygous mutation of ENG gene C.1361T>C (p.Leu454Pro) is a novel mutation site in ENG gene, which has not been reported in gnomAD database, clinvar database, ESP database,Thousand Genomes Project database and EXAC database. The novel mutation site of ENG gene extended the gene variation spectrum of HHT pathogenic genes.