Objective: The search for rapid and effective early diagnostic markers of hypotharyn-geal carcinoma becomes particularly critical and important. Therefore, we explored the value of cir-culating expression of non-coding RNAs for the diagnosis of early hypotharyngeal cancer.Methods: After screening HPSCC-related research data in the NCBI-GEO database, the practi-cal report extraction language (Perl) was used to give genes different biotype attributes. The R lan-guage limma package was utilized to analyze the differential expression of lncRNAs and mRNAs, respectively.The quantitative RT-PCR (Reverse transcription-polymerase chain reaction) analysis were performed to determine the plasma expression levels of non-coding RNAsResults: Compared with the control groups, the differential expression of 137 lncRNAs and 297 mRNAs in the plasma of HPSCC patients was statistically significant. There were 32 differentially expressed lncRNAs, 19 differentially expressed mRNAs. The score of LncRNA AC018761 + miR-488 was AUC = 0.846, the best cut-off value was > 40 points, the sensitivity was 74.58%, and the specificity was 79.88%.Conclusion: Our results indicated that the over-expression of lncRNA-AC018761 and miR-488 were significantly up-regulated in serum of patients with HPSCC. Therefore, lncRNA-AC018761 and miR-488 maybe the non-invasive independent predictor for early HPSCC with high sensitivity and specificity.(c) 2023 The Authors. Published by Elsevier B.V. on behalf of King Saud University. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).