BackgroundHead and neck squamous cell carcinoma (HNSC) is one of the most common malignancies, and identification of HNSC biomarkers is critical. LIM Domain And Actin Binding 1 (LIMA1) is involved in actin cytoskeleton regulation and dynamics. The role of LIMA1 in HNSC is unclear. This is the first study to investigate the expression of LIMA1 in HNSC patients and its prognostic value, potential biological functions, and impact on the immune system.MethodsGene expression and clinicopathological analysis, enrichment analysis, and immune infiltration analysis were all based on data from The Cancer Genome Atlas (TCGA) with additional bioinformatics analysis. Statistical analysis was performed using TIMER and ssGSEA to analyze the immune response to LIMA1 expression in HNSCs. In addition, Gene Expression Omnibus (GEO), Kaplan–Meier(K-M) survival analysis, and data from the Human Protein Atlas (HPA) were used to validate the results.ResultsLIMA1 played a key role as an independent prognostic factor in HNSC patients. GSEA found that LIMA1 is associated with promoting cell adhesion and suppressing immune function. LIMA1 expression was significantly correlated with infiltration of B cells, CD8+ T cells, CD4+ T cells, dendritic cells, and neutrophils and was coexpressed with immune-related genes and immune checkpoints.ConclusionThe expression of LIMA1 is increased in HNSC, and the high expression of LIMA1 is associated with poor prognosis. LIMA1 may affect tumor development by regulating tumor-infiltrating cells in the tumor microenvironment (TME). LIMA1 may be a potential target for immunotherapy.