The ubiquitin-like with PHD and ring finger domains 1 (UHRF1) has been reported to be essential for cell proliferation and plays a critical role in the development and progression of many human carcinomas. However, its clinical and prognostic significance in laryngeal squamous cell carcinoma (LSCC) remains unclear. In the current study, 60 patients with LSCC were studied. UHRF1 expression at mRNA and protein levels was detected by quantitative reverse transcriptase-polymerase chain reaction (qRT-PCR) and immunohistochemistry, respectively, in both tissues of LSCC and corresponding adjacent normal larynx tissues. Statistical analyses were conducted to test the correlations between UHRF1 expression, clinicopathological parameters, and prognosis. qRT-PCR showed that the expression of UHRF1 mRNA in LSCC tissues was significantly higher than that in adjacent normal larynx tissues (P 0.05). Overexpression of UHRF1 was also associated with worse overall survival examined by Kaplan-Meier method (P = 0.036). Multivariate analysis showed that increased expression of UHRF1 was an independent prognostic factor for LSCC (P = 0.013). Therefore, overexpression of UHRF1 may play an important role in the development and progression of LSCC, and UHRF1 might be a useful biomarker for the prognosis of LSCC.