SIAH is widely expressed in lot of kinds of tumors. It plays a significant role in human cancer, but its clinicopathologic and prognostic significance in laryngeal squamous cell carcinoma (LSCC) has not yet been elucidated. The SIAH expression was examined at mRNA and protein levels by real-time quantitative polymerase chain reaction (RT-PCR), Western blotting, and immunohistochemistry in LSCC tissues and adjacent normal larynx tissues. Statistical analyses were applied to test the associations between SIAH expression, clinicopathologic factors, and prognosis. Western blots and RT-PCR showed that the expression level of SIAH was lower in LSCC tissues than in adjacent normal larynx tissues. By immunohistochemical analysis, reduced expression of SIAH was found in 71.67 % LSCCs. After multivariate analysis, along with pathologic differentiation, the protein expression level of SIAH was an independent and significant predictive factor (P = 0.04). Furthermore, patients with SIAH-low tumors had a shorter disease-free survival and overall survival (P = 0.002 and P = 0.045, respectively). Our study suggests that SIAH protein expression is a valuable biomarker for LSCC. Low expression of SIAH is associated with poor disease-free survival and overall survival in LSCC patients.