Purpose To investigate the profiles and factors influencing serum IgG4 levels and evaluate the diagnostic value of serum IgG4 in IgG4-related CRS. Methods This was a prospective study analyzing data from 288 hospitalized CRS patients who had undergone endoscopic sinus surgery from July 1, 2017 to August 31, 2018. Data were analyzed for correlations between elevated serum IgG4 concentrations (> 135 mg/dL) and clinical symptoms (nasal congestion, rhinorrhea, loss of smell, headache and/or facial pain), endoscopic presentation (Lund-Kennedy scores), allergic status (total and allergen-specific IgE), and pathological features (IgG4+ and IgG+ cells). Results Overall, 43/288 (14.9%) CRS patients had elevated serum IgG4 levels > 135 mg/dL. Comparison of the clinical parameters between patients with elevated and normal serum IgG4 levels demonstrated serum total IgE levels to be significantly different (P = 0.003) between the two groups; and significantly correlated with serum IgG4 level in CRS subjects (P = 0.000; r = 0.232), particularly CRS patients with nasal polyps (P = 0.000; r = 0.259). In contrast, the ratio of plasmocyte/inflammatory cells and IgG4+ cells/IgG+ plasmocytes, and IgG4+ plasma cells/HPF in sinus mucosa were not significantly different between the groups and no patient with elevated serum IgG4 demonstrated ratio of IgG4+ /IgG+ cells > 40% or > 10 IgG4+ plasma cells/HPF. Conclusion Serum IgG4 concentration is not related to the clinical phenotype of CRS and is likely to be of limited value when used alone in the diagnosis of IgG4-related CRS.