The nuclear factor-κ;B (NF-κ;B) signaling pathway has been studied extensively in mammalians and insects but has been less well investigated in marine molluscs. Inhibitor of κ;B (Iκ;B), an important component of the NF-κ;B signaling pathway, serves as a crucial mediator of the innate immune system. A homolog of Iκ;B was identified in a razor clam (Solen grandis), designated as SgIκ;B, and its messenger RNA expression was detected both in tissues and towards pathogen-associated molecular patterns. Full-length complementaryDNAof SgIκ;B is 2,232 bp, containing a 181-bp 5′ untranslated region (UTR) and a 970-bp 3# UTR with a poly (A) tail. The open reading frame is 1,080 bp, encoding a 359-amino acid polypeptide with a predicted molecular weight of 40.1 kDa and an isoelectric point of 4.88. A potential PEST motif (E2SNDLEMDTCPLEMDS17) and the Iκ;B degradation motif (ES44GYKS48) are located at the N-terminus, and 2 conserved casein kinase II phosphorylation sites (S337DEE340 and S346YDD349) exist at the C terminus. The presence of 6 conserved ankyrin repeats in SgIκ;B and its close phylogenetic relationship with other IχBs strongly suggest that SgIκ;B belongs to the IχB superfamily. Messenger RNA of SgIκ;B is expressed constitutively in various tissues of healthy S. grandis, with the greatest expression in gill and hepatopancreas, followed by gonad, mantle, hemocyte, and muscle in descending order. Messenger RNA expression of SgIκ;B in hemocytes is upregulated significantly to varying degrees (P < 0.01) on stimulation with lipopolysaccharide, peptidoglycan, and β-1,3-glucan. The results indicate the existence of a NF-κ;B signaling pathway in S. grandis and provide evidence for possible regulatory mechanisms during an immune challenge.