Objectives: SET Domain Containing Protein 8 (SET8), a member of the SET domain containing methyltransferase family involved in several biological processes and SET8 expression levels, reportedly affects the outcomes of patients with breast cancer, renal cancer, prostate carcinoma, and oesophageal squamous cell carcinoma. However, there have been no relevant studies on the biofunction and use of SET8 expression in the prediction of laryngeal squamous cell carcinoma (LSCC) outcomes.Methods: In our study, SET8 expression levels were detected using immunohistochemical staining, western blotting, and quantitative real-time RT-PCR (qRT-PCR) with semi quantitative analysis for laryngeal cancer outcomes. Additionally, we assessed the influence of SET8 on the behaviour of laryngeal cancer cells in vitro, using cell counting kit-8, clone formation, wound healing, and Transwell invasion assays. We subsequently performed qRT-PCR and western blotting for an in-depth study of SET8.Results: Our study showed marked upregulation of SET8 in tumour tissues and laryngeal cancer cell lines. High SET8 expression predicts poor prognosis in patients with LSCC, and its expression can be used as an independent predictor of LSCC outcome. Subsequent functional analyses indicated that SET8 knockdown exerted an inhibitory effect on proliferation, migration, and invasiveness in vitro.Conclusions: SET8 may be associated with epithelialmesenchymal transition. Our results demonstrate that higher SET8 expression is an unfavourable prognostic predictor and exerts tumour-promoting effects in LSCC.