Objective Activation of mast cells associates with eosinophilic inflammation in chronic rhinosinusitis with nasal polyps (CRSwNP). The disease-specific mast cell-triggering mechanisms apart from immunoglobulin E are poorly understood in CRSwNP. CD30L/CD30 are members of the tumor necrosis factor/receptor superfamily and display immune modulatory function on mast cells. The aim of this study was to explore the expression and function of CD30 and CD30L in CRSwNP. Methods The mRNA expression of CD30 and CD30L was analyzed by real-time polymerase chain reaction. The cellular expression of CD30L was determined by immunofluorescence staining. The soluble CD30 levels in nasal tissues were detected by enzyme-linked immunosorbent assay. HMC-1 cells, a human mast cell line, were cultured and stimulated with CD30. Results Compared with control tissues, CD30 mRNA expression levels were increased in eosinophilic polyps, and soluble CD30 protein levels were upregulated in both eosinophilic and noneosinophilic polyps with a greater increase in eosinophilic type. CD30 was expressed by T cells and B cells in nasal polyps. The CD30L mRNA expression levels and the number of CD30L(+) cells and CD30L(+)tryptase(+) mast cells were increased in eosinophilic polyps but not in noneosinophilic polyps as compared with control tissues. Mast cells accounted for 60% of CD30L(+) cells in eosinophilic polyps. CD30 induced HMC-1 cells to produce interleukin (IL)-4 and IL-13 without degranulation. Mast cells expressed IL-4 and IL-13 in eosinophilic polyps. The number of CD30L(+)tryptase(+) mast cells was positively correlated with the number of eosinophils and total inflammatory cells in eosinophilic polyps. Conclusion CD30/CD30L-mediated mast cell activation may promote the eosinophilic inflammation in CRSwNP.