Background: Tissue eosinophils have been shown to be associated with polyp recurrence in chronic rhinosinusitis with nasal polyps (CRSwNP). We addressed whether the mRNA levels of Charcot-Leyden Crystal (CLC) in nasal brushing samples, a molecule mainly released from activated eosinophils, could serve as an effective non-invasive biomarker to predict polyp recurrence. Methods: A total of 51 patients with CRSwNP completing the postoperative follow-up over a period of 12-18 months were enrolled. Baseline CLC mRNA levels of the nasal brushings collected prior to endoscopic sinus surgery were quantified by quantitative real-time polymerase chain reaction (qRT-PCR). Polyp specimens were collected during surgery and were evaluated for inflammatory cells by histopathologic staining. The patients' baseline characteristics were reviewed and analyzed for associations with recurrence. Logistic regression analysis was performed to determine the predictive factors for polyp recurrence, and receiver operating characteristic (ROC) curves were performed to determine their predictive values. Results: Overall, 25/51(49.02%) patients experienced polyp recurrence during the 12-18 months follow-up. The baseline relative CLC mRNA level in nasal brushing samples was significantly increased in patients with recurrence compared to those without recurrence (p<0.001). ROC curves demonstrated that a cut-off value of -6.419 for the relative CLC mRNA level normalized to GAPDH in nasal brushings predicted the recurrence with 92.00% sensitivities and 88.46% specificities (AUC=0.932, p<0.001). Conclusions: The relative CLC mRNA levels in nasal brushings may serve as a reliable non-invasive biomarker to predict CRSwNP recurrence.