OBJECTIVE There are few ideal predictors used to evaluate the prognosis of laryngeal squamous cell carcinoma (LSCC). This study was designed to investigate the expression of p73 and PTEN (phosphates and tension homolog deleted on chromosome ten) and their association with clinical, histologic characteristics and prognosis in LSCC. METHODS p73 protein and PTEN protein were examined by using immunochistochemical SABC staining method in 65 cases of LSCC and in 23 cases of para-tumor tissues. RESULTS p73 protein and PTEN protein in LSCC showed positive expression of about 58.5% (38/65) and 49.2% (32/65), compared to para-tumor tissues of about 17.4% (4/23) and 95.7% (22/23) with statistical significance (P< 0.05). p73 protein positive expression showed stronger in stage III-IV of LSCC than that in stage I-II (P< 0.05); it more often appeared in recurrent cases than in primary cases (P< 0.05). And p73 protein positive expression with distant metastasis was stronger than that in LSCC without distant metastasis (P< 0.05). PTEN protein positive expression was stronger in stage I-II of LSCC than that in stage III-IV (P< 0.05); PTEN protein positive expression appears less frequently in poor differentiation of LSCC, compared to well/moderate differentiation (P< 0.05); PTEN positive expression in cases with cervical lymph node metastasis and distant metastasis was lower than that in those without metastasis (P< 0.05). PTEN expression showed significantly stronger in the patients whose survival time over 5 years (66.7%) than in the patients whose survival time was less than 5 years (27.3%) (P< 0.05). CONCLUSIONS PTEN positive expression may be useful for predicting the prognosis of LSCC.