We conducted a study to validate the expression of PLUNC (palate, lung, and nasal epithelial clone) protein in nasal polyp and chronic sinusitis tissue by immunohistochemistry. We also explored the relationship between the intensity of positive immunohistochemical staining for PLUNC protein and postoperative therapeutic efficacy. Our study population consisted of 34 patients with nasal polyps and 30 with chronic sinusitis who had undergone surgical treatment, along with 18 healthy controls who did not undergo surgery. All samples were stained according to the streptavidin-peroxidase immunohistochemical method to examine PLUNC protein expression. The surgical patients were evaluated for clinical therapeutic efficacy 6 months postoperatively. The association between efficacy and the intensity of PLUNC protein positivity was examined by the Spearman rank correlation analysis. Intensity was rated as either +++ (>50% positive cells), ++ (26 to 50% positive cells), + (<= 25% positive cells), or - (no positive cells). We found that the most common levels of PLUNC positivity were + in the patients with nasal polyps, +++ in the patients with chronic sinusitis, and ++ in the controls (p < 0.01). Analysis of the Spearman rank correlation indicated that the intensity of PLUNC protein expression was significantly correlated with postoperative therapeutic efficacy (p < 0.001). We conclude that PLUNC protein is an essential factor in the innate defense mechanism of the nasal mucosa. The immunohistochemical staining of PLUNC protein could have clinical benefit in terms of predicting therapeutic efficacy and outcomes in patients with nasal polyps or chronic sinusitis.