BackgroundLong non-coding RNAs (lncRNAs) are increasingly recognized as essential players in various biological processes due to their interactions with DNA, RNA, and protein. Emerging studies have demonstrated lncRNAs as prognostic biomarkers in multiple cancers. However, the prognostic effect of lncRNA AL161431.1 in head and neck squamous cell carcinoma (HNSCC) patients has not been reported.MethodsIn the present study, we conducted a series of analyses to identify and validate the prognostic value of lncRNA AL161431.1 in HNSCC, which included differential lncRNAs screening, survival analysis, Cox regression analysis, time ROCanalysis, nomogram prediction, enrichment analysis, tumor infiltration of immune cells, drug sensitivity analysis, and quantitative real-time polymerase chain reaction (qRT-PCR).ResultsIn this study, we performed a comprehensive survival and predictive analysis and demonstrated that AL161431.1 was an independent prognostic factor of HNSCC, for which a high AL161431.1 level indicated poor survival in HNSCC. Functional enrichment analyses found that cell growth and immune-related pathways were significantly enriched in HNSCC, suggesting that AL161431.1 may play a role in tumor development and tumor microenvironment (TME). AL161431.1-related immune cells infiltration analysis demonstrated that AL161431.1 expression is significantly positively associated with M0 macrophages in HNSCC (P<0.001). Using "OncoPredict", we recognized chemotherapy drugs sensitive to the high expression group. Quantitative real-time polymerase chain reaction (qRT-PCR) was performed to identify the expression level of AL161431.1 in HNSCC, and the results further validated our findings.ConclusionsOur findings suggest that AL161431.1 is a reliable prognostic marker for HNSCC and can potentially be an effective therapeutic target.