Houttuynia cordata Thunb (HCT) is widely used in oriental medicine as a remedy for inflammation. However, at present there is no explanation for the mechanism by which HCT affects the production of inflammatory cytokines. The current study aimed to determine the effect of an essence extracted from HCT on mast cell-mediated inflammatory responses. Inflammatory cytokine production induced by phorbol myristate acetate (PMA) plus a calcium ionophore, A23187, was measured in the human mast cell line, HMC-1, incubated with various concentrations of HCT. TNF-α, IL-6 and IL-8 secreted protein levels were measured using an ELISA assay. TNF-α, IL-6 and IL-8 mRNA levels were measured using RT-PCR analysis. Nuclear and cytoplasmic proteins were examined by western blot analysis. The NF-κB promoter activity was examined by luciferase assay. It was observed that HCT inhibited PMA plus A23187-induced TNF-α and IL-6 secretion and reduced the mRNA levels of TNF-α, IL-6 and IL-8. It was also noted that HCT suppressed the induction of NF-κB activity, inhibited nuclear translocation of NF-κB and blocked the phosphorylation of IκBα in stimulated HMC-1 cells. It was concluded that HCT is an inhibitor of NF-κB and cytokines blocking mast cell-mediated inflammatory responses. These results indicate that HCT may be used for the treatment of mast cell-derived allergic inflammatory diseases.