Conclusion: HDAC1 may be a prognostic biomarker for LSCC malignant potency and a potent factor resulting in decreased sensitivity of LSCC in radiotherapy. Objective: The aim of this study was to evaluate the correlation between histone deacetylase 1 (HDAC1) over-expression and clinical features in laryngeal squamous cell carcinoma (LSCC). Methods: This study assessed the HDAC1 expressions in 90 formalin-fixed paraffin-embedded LSCC samples, 30 adjacent non-neoplastic tissues, and 30 laryngeal polyp tissues by immunohistochemistry (IHC). In addition, another 40 LSCC samples were collected that were divided into two groups after 3-month radiotherapy: the high radio-sensitive group (HRS) and low radio-sensitive group (LRS). Overall survival curves of all the LSCC patients were constructed by Kaplan–Meier method and long-rank test. Results: All ninety samples were positively immunostained for HDAC1. The expression of HDAC1 was up-regulated and significantly associated with T classification, lymph node metastases, tumor location and clinical stage. HDAC1 was mainly labeled in the epithelial cells of laryngeal polyp tissues and adjacent non-neoplastic tissues. In addition, the expression of HDAC1 was significantly higher in LRS than that in HRS. The positive rates for stage III-IV tumor were significantly higher than those for stage II. LSCC patients with HDAC1 over-expression and LRS presented a shorter 5-year overall survival rate.