Introduction: Head and neck squamous cell carcinoma (HNSCC) is an aggressive life-threatening disease associated with high mortality rates. Heterogeneous nuclear ribonucleoprotein A2B1 (HNRNPA2B1) is tightly linked to tumorigenesis. Recent studies have shown that HNRNPA2B1 is a mediator of N6-methyladenosine (m6A)-dependent nuclear RNA processing events. However, the role of HNRNPA2B1 in head and neck squamous cell carcinoma (HNSCC) is largely unknown. Objective: To check the expression profile for HNRNPA2B1 in HNSCC using the Oncomine datasets and TIMER database. Methods: Therefore, in the present study, we used the large TCGA RNA sequencing (RNAseq) dataset to explore the HNRNPA2B1 expression level in HNSCC. We also used Kaplan-Meier plotter to evaluate the effect of HNRNPA2B1 on clinical prognosis. Results: HNRNPA2B1 was significantly upregulated in HNSCC compared to normal tissues (p__ampersandsignlt;0.05). Moreover, the increased expression of HNRNPA2B1 mRNA was closely associated with reduced overall survival (OS) (p=0.0099) in HNSCC patients. Conclusion: Our findings systematically elucidate the expression profiles and instinct prognostic value of HNRNPA2B1 in HNSCC, which might provide a novel therapeutic target and potential prognostic biomarker for HNSCC patients.