Objective: To analyze the correlation between the expression of Integrin α5 (ITGA5) and prognosis of head and neck squamous cell carcinoma (HNSCC). Methods: The RNA-seq data and relevant clinical follow-up information of HNSCC in TCGA database were used to establish mRNA spectrum for variation analysis, further verification was conducted in GEO databases. Results: The mRNA expression of ITGA5 was found significantly higher in tumor tissues compared to normal tissues, and the overall survival of patients by Kaplan‐Meier analyses in ITGA5 high-expression group was notably shortened(P<0.050). The expression level of ITGA5 could be treated as an independent prognostic indicator since it was verified in GEO databases to be sensitive and specific for patient survival and prognosis. Conclusion: ITGA5 is closely related to the survival and prognosis of HNSCC patients and may serve as a novel prognostic biomarker.