Aims: Chronic rhinosinusitis (CRS) is a common pediatric disease characterized by chronic mucosal infection. Among the related diseases of CRS, cystic fibrosis (CF) is caused by mutations in the Cystic Fibrosis Transmembrane Conductance Regulator (CFTR) gene, resulting in the absence or dysfunction of CFTR protein. However, the prevalence of CFTR variants in the Chinese population is not well understood. The purpose of this study is to investigate the frequency and sites of CFTR mutations in Chinese children with CRS and to analyze their relationship with CRS susceptibility. Methodology: Whole-exome sequencing of the CFTR gene was performed on 106 CRS children from mainland China. Software tools such as SIFT, Polyphen V2, and Splice AI were used to predict the pathogenicity of mutations in introns and exons. The three-dimensional structure of the protein was also modeled for functional prediction. Results: A total of 31 CFTR variants were detected, with the carrier frequency of 7 sites significantly higher than that in the population database.Nine sites were located in important functional domains of the CFTR protein, potentially affecting ion transmembrane transport and protein activation. 37 individuals carried non-SNP mutations, of which 91.89% had a history of recurrent upper respiratory tract infections, 16 patients were diagnosed with nasal polyps, 5 patients were diagnosed with bronchiectasis, and 1 patient was diagnosed with CF-related diseases. Conclusion: The frequency of CFTR mutations in Chinese children with CRS is elevated, with mutation sites differing from those in Caucasians. The mutation sites with the highest frequency arep.I556V, p.E217G, and c.1210-12[T].Carrying multiple CFTR mutations, especially p.E217G, p.I807 M, p.V920L, and c.1210-12[T], may increase the susceptibility to CRS. Therefore, children with refractory CRS require CFTR gene testing and investigation for CFTR variant-related diseases to understand the potential for CF.