Background: Chronic rhinosinusitis with nasal polyps (CRSwNP) is a heterogeneous disease with different clinical characteristics and different treatment responsiveness. The aims of this study were to compare the nasal fluid cytology and cytokines between eosinophilic CRSwNP (eCRSwNP) and non-eosinophilic CRSwNP (neCRSwNP) and establish a new multivariate model to predict eCRSwNP before surgery to improve personalized treatment for CRSwNP patients.Methods: Eighty-six consecutive patients with CRSwNP and sixteen healthy controls were recruited in this study. Nasal fluid (NF) was collected from all subjects and nasal polyp tissue was collected during the surgery. The differential cell counts and concentrations of IL-6, IL-8, TNF-α and IL-10 in NF were measured. Univariate and multivariate logistic regression were used to identify predictors for eCRSwNP.Results: There were more inflammatory cells in NF of CRSwNP than controls. The eosinophil percentage was significantly higher in eCRSwNP than neCRSwNP and controls. The level of IL-8 was significantly higher in neCRSwNP than in eCRSwNP and controls.Blood eosinophilia, nasal fluid eosinophilia, higher total ethmoid score / total maxillary score (E/M ratio) and higher visual analogue scale (VAS) score of CRS were associated with eCRSwNP, the area under receiver operating characteristic curve (AUC) was 0.800, 0.755, 0.703 and 0.648, respectively. Using the coefficients of multivariate regression, we set up a scoring system to predict eCRSwNP with three of the variates and the AUC was 0.883. Conclusion:ECRSwNP, neCRSwNP and healthy controls demonstrated different cytology and cytokine profiles in NF. A new preoperational multivariate prediction model for eCRSwNP with NF eosinophilia, blood eosinophilia and higher E/M ratio was established.