Objectives We aimed to confirm the presence of pepsinA in the nasal secretions and tissues of chronic rhinosinusitis (CRS) patients and reveal the relationship between CRS and laryngopharyngeal reflux (LPR). Study Design Cross-sectional study. Setting The study was conducted at the Department of Oto-Rhino-Laryngology, West China Hospital, Sichuan University. Subjects and Methods A total of 32 CRS patients with or without nasal polyps (CRSwNP and CRSsNP, respectively) and 10 normal controls were enrolled in our study. We investigated the expression of pepsinA in the nasal tissues, secretions, and blood plasma from the subjects by immunohistochemical staining, Western blot, or ELISA. Additionally, the expressions of MUC4, MUC5AC, MUC5B, MUC8, and pepsinogenA in nasal tissue were evaluated by quantitative real-time polymerase chain reaction. Results Immunohistochemistry and Western blot revealed that the pepsinA expression levels in the turbinate mucosa in CRSwNP/CRSsNP patients, which were largely restricted to the epithelial layer or glandular mucous cells in nasal tissues, were significantly higher than those in controls and in the polyp tissues of CRSwNP patients (P < .05). In addition, the concentration of pepsinA in nasal secretions was significantly increased in the CRSwNP (147.85 53.69 ng/mL, P < .001) and CRSsNP (134.12 +/- 36.23 ng/mL, P < .001) groups as compared with the controls (68.69 +/- 19.28 ng/mL). Although MUC5AC, MUC5B, and MUC8 expression differed among the groups, no correlation between pepsinA and mucin genes was found. Conclusion The results of this study provided evidence of an association between LPR and CRS, although no correlation was found to exist between LPR and mucin genes in CRS patients.