Background: Novel prognostic biomarkers or therapeutic molecular targets for laryngeal squamous cell carcinoma (LSCC) are an urgent priority. We here sought to identify multiple novel LSCC-associated genes. Methods: Using high-density microarray expression profiling, we identified multiple genes that were significantly altered between human LSCCs and paired normal tissues. Potential oncogenic functions of one such gene, DCUN1D5, were further characterized in vitro. Results: Our results demonstrated that DCUN1D5 was highly expressed in LSCCs. Overexpression of DCUN1D5 in vitro resulted in 2.7-fold increased cellular migration, 67.5% increased invasive capacity, and 2.6-fold increased proliferation. Endogenous DCUN1D5 expression was decreased in a time-dependent manner after genotoxic stress, and silencing of DCUN1D5 by siRNA decreased the number of cells in the S phase by 10.2% and increased apoptosis by 11.7%. Conclusion: Our data suggest that DCUN1D5 in vitro might have vital roles in DNA damage response, but further studies are warranted to assess its significance in vivo.