Chronic rhinosinusitis with nasal polyps (CRSwNP) is a common health problem in the world. However, its etiology remains unclear. Recent researches have hypothesized that Staphylococcus aureus (SA) exotoxins which act as superantigens might be associated with inflammatory mucosal changes seen in CRSwNP. The objective of this study is to evaluate the relationship between Staphylococcus aureus superantigens and CRSwNP. PubMed, MEDLINE, EMBASE, Cochrane Library and CNKI were searched to collect the case-control studies on the relationship between SA superantigens and CRSwNP from the date of establishment of the databases to May 2013. The extracted data were analyzed by RevMan 5.0. The main outcome measures were SA culture-positive rate, the detection rate of SA superantigens and its specific IgE. Twelve studies including 340 cases and 178 controls were selected. The results showed that SA culture-positive rate in the CRSwNP group was significantly higher than that in the control group (OR 4.85, 95% CI 1.80-13.05, P = 0.002), the detection rate of SA superantigens and its specific IgE in the CRSwNP group were both significantly higher than that in the control group (OR 12.07, 95% CI 4.57-31.90, P < 0.00001; OR 17.03, 95% CI 5.43-53.39, P < 0.00001, respectively) and the CD4(+) T cell counts and Lund-Mackay CT scores were statistically higher in the IgE-positive group than in the IgE-negative group (MD 16.26, 95% CI 4.86-27.67, P = 0.005, MD 2.43, 95 % CI 0.39-4.48, P = 0.02, respectively). However, the eosinophil and CD8(+) T cell counts showed no difference between IgE-positive group and -negative group. This meta-analysis indicated that the SA superantigens may be a risk factor for CRSwNP, and the presence of SA superantigen is related to the disease severity of CRSwNP.