Objective To investigate the correlation between serum interleukin-17 A (IL-17 A), interferon-gamma (IFN-γ), and the severity of chronic rhinosinusitis with nasal polyps (CRSwNP) . Methods A prospective study was conducted on 82 patients with CRSwNP admitted to the First Affiliated Hospital of Henan University of Science and Technology from June 2021 to June 2023 as the observation group, and 30 patients with isolated nasal septal deviation during the same period as the control group. Before treatment, serum levels of IL-17 A, IFN-γ, transforming growth factor-beta 1 (TGF-β1), and matrix metalloproteinase-9 (MMP-9) were measured and compared between the two groups. Pearson correlation analysis was used to assess the correlation between serum IL-17 A, IFN-γ, the severity of the disease, and serum TGF-β1, MMP-9. Receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic efficiency of serum IL-17 A and IFN-γ for CRSwNP. Results The serum levels of IL-17 A, IFN-γ, TGF-β1, and MMP-9 in the observation group were significantly higher than those in the control group, with statistical significance (P<0.05) . The Lund-Mackay score and Lund-Kennedy score in the observation group were significantly higher than those in the control group (P<0.05) . Pearson correlation analysis showed a positive correlation between serum IL-17 A, IFN-γ levels, Lund-Mackay score, Lund-Kennedy score, serum TGF-β1, and MMP-9 in CRSwNP patients (P<0.05) . ROC curve analysis demonstrated that serum IL-17 A, IFN-γ, and their combined detection had diagnostic efficiency for CRSwNP (P<0.05) . The combined detection showed higher efficiency than individual testing, with an AUC of 0.953, sensitivity of 93.90%, and specificity of 90.00%. Conclusion Elevated levels of IL-17 A and IFN-γ are associated with the occurrence of CRSwNP, and their levels correlate with the severity of the disease and nasal mucosal tissue remodeling. They can serve as early diagnostic indicators for CRSwNP. [ABSTRACT FROM AUTHOR]