Head and neck squamous cell carcinoma (HNSC) is one of the most common cancer types in the world. The study in molecular markers for HNSC prognosis is of great significance. We hypothesized that Aminoacyl tRNA Synthetase Complex Interacting Multifunctional Protein 1 (AIMP1), a gene that encodes a cytokine, is a critical biomarker for HNSC.We acquired clinical data, mRNA expression data, protein staining data, and single-cell expression data of HNSC from open databases and evaluated the clinical prognostic value of AIMP1, and explored the potential roles of AIMP1 in HNSC biology and tumor immune microenvironment.AIMP1 was overexpressed in HNSC compared to normal tissues. Higher AIMP1 expression was associated with a worse survival rate. A survival nomogram was constructed for HNSC patients. One thousand two hundred and eighty-one genes were identified as positively associated with AIMP1 and enriched in proliferation-related terminologies, while 303 genes were identified as negatively associated with AIMP1 and enriched in terminologies related to skin development and immune cell regulation. AIMP1 was positively correlated with stemness, cell cycle, and DNA repair, and negatively correlated with angiogenesis, quiescence, metastasis, hypoxia, inflammation, EMT, DNA damage, and invasion in single cells. AIMP1 was expressed higher in malignant cells than immune cells and there was no difference in AIMP1 expression among immune cell types. AIMP1 high group had a lower immune score, stroma score, and microenvironment score.AIMP1 is a potential diagnostic and prognostic biomarker for HNSC patients and can potentially affect the proliferation and tumor immune microenvironment of HNSC cells. This study provided a novel molecular marker for the improvement of clinical HNSC treatment.