Background5-Methylcytosine (m5C) methylation is recognized as an mRNA modification that participates in biological progression by regulating related lncRNAs. In this research, we explored the relationship between m5C-related lncRNAs (mrlncRNAs) and head and neck squamous cell carcinoma (HNSCC) to establish a predictive model.MethodsRNA sequencing and related information were obtained from the TCGA database, and patients were divided into two sets to establish and verify the risk model while identifying prognostic mrlncRNAs. Areas under the ROC curves were assessed to evaluate the predictive effectiveness, and a predictive nomogram was constructed for further prediction. Subsequently, the tumor mutation burden (TMB), stemness, functional enrichment analysis, tumor microenvironment, and immunotherapeutic and chemotherapeutic responses were also assessed based on this novel risk model. Moreover, patients were regrouped into subtypes according to the expression of model mrlncRNAs.ResultsAssessed by the predictive risk model, patients were distinguished into the low-MLRS and high-MLRS groups, showing satisfactory predictive effects with AUCs of 0.673, 0.712, and 0.681 for the ROCs, respectively. Patients in the low-MLRS groups exhibited better survival status, lower mutated frequency, and lower stemness but were more sensitive to immunotherapeutic response, whereas the high-MLRS group appeared to have higher sensitivity to chemotherapy. Subsequently, patients were regrouped into two clusters: cluster 1 displayed immunosuppressive status, but cluster 2 behaved as a hot tumor with a better immunotherapeutic response.ConclusionsReferring to the above results, we established a m5C-related lncRNA model to evaluate the prognosis, TME, TMB, and clinical treatments for HNSCC patients. This novel assessment system is able to precisely predict the patients’ prognosis and identify hot and cold tumor subtypes clearly for HNSCC patients, providing ideas for clinical treatment.Supplementary InformationThe online version contains supplementary material available at 10.1186/s12957-023-03067-w.