To explore the association between the levels of cyclooxygenase-2 (COX-2), aquaporin-1 (AQP1), pepsinogen I (PGI), and gastrin-17 (G17) and pathological features of laryngeal cancer (LC).Clinical data of 120 patients with LC, treated in Shanghai Jiao Tong University School of Medicine from May 2022 to May 2023, as well as 120 healthy individuals who underwent physical examinations during the same period, were retrospectively analyzed. Serum levels of COX-2, AQP1, PGI, and G17 of LC patients and the healthy cohort were compared, and their association with pathological features of LC was investigated.LC was associated with significantly higher serum levels of COX-2, AQP1, and G17 and lower of PGI compared to the control group (P<0.05). Levels of COX-2, AQP1, and G17 positively correlated with the tumor, node and metastasis (TNM) staging, infiltration depth, and the lymph node metastases, and negatively correlated with the degree of differentiation (P<0.05). There was a significant negative correlation between the level of PGI and TNM staging, infiltration depth, and lymph node metastases. PG1 also positively correlated with the degree of differentiation (P<0.05). Area under curve (AUC) of combined COX-2, AQP1, PG-I, and G17 was significantly higher than that of each index alone (P<0.05).Levels of COX-2, AQP1, PGI, and G17 showed significant association with specific pathological features of LC. Serum levels of COX-2, AQP1, PGI, and G17 have certain predictive value for LC, and the combined predictive value of these four indicators is higher than that of a single indicator.Copyright: © Pakistan Journal of Medical Sciences.