Background: To evaluate the association of MMP11 and P14(ARF) expression in laryngeal squamous cell carcinoma (LSCC) with clinical pathological characteristics and survival. Methods: The mRNA and protein levels for both genes were determined in 65 LSCC patients. A log-rank test and Cox models were used to compare survival among different groups. Results: The mRNA expressions of MMP11 and P14(ARF) were significantly different between LSCC and their corresponding adjacent tissues (All P < 0.001). The expressions of MMP11 and P14(ARF) were correlated with several clinical characteristics (All P < 0.05). Patients with low MMP11 and high P14(ARF) expression had significantly better survival compared with those with high MMP11 and low P14(ARF) expression, respectively (All P < 0.05). The patients with surgery only had significantly better survival than those with chemoradiotherapy (log rank: P = 0.016), particularly in patients with low MMP11 and high P14(ARF) expression (log rank: P = 0.006). Furthermore, multivariable analysis showed that patients with low MMP11 and high P14(ARF) expression alone had a significantly reduced risk of death compared with those with high MMP11 and low P14(ARF) expression. The reduced risk for overall death was pronounced for patients with low and high expression of both genes (HR, 0.2; 95% CI, 0.1-0.5) compared with any other co-expression status of both genes, particularly for patients with surgery only (HR, 0.1; 95% CI, 0.00.9). Conclusion: These results suggest that altered expression of MMP11 and P14(ARF) in tumors may individually, or in combination, predict poor prognosis of LSCC, particularly for patients with surgery only.