Aim: To explore the biological functions and clinicopathologic significance of the long noncoding RNA KTN1-AS1 in head and neck squamous cell carcinoma (HNSCC). Materials & methods: We assessed the effects of KTN1-AS1 and identified the target miRNA by bioinformatics analysis, luciferase reporter, RNA pull-down and RNA immunoprecipitation assays. The clinicopathologic features of KTN1-AS1 and its target miRNA were analyzed in HNSCC. Results: KTN1-AS1, a competing endogenous RNA, promoted cell proliferation, migration, invasion and epithelial-mesenchymal transition by sponging miR-153-3p in HNSCC. Dysregulation of SNAI1 and ZEB2 mediated the effect of KTN1-AS1 due to miR-153-3p exhaustion. The KTN1-AS1 and miR-153-3p combination can accurately diagnose HNSCC. Conclusion: The KTN1-AS1 and miR-153-3p combination could be a valuable diagnostic and prognostic predictor for HNSCC.