Barnacles are notorious marine fouling organisms. Their successful attachment to a substrate requires that they search for an appropriate habitat during their cyprid stage. A chemical cue called SIPC (Set-tlement-Inducing Protein Complex) has been shown to play a key role in the induction of cyprid gregarious settlement; however, the underlying biochemical mechanism remains unclear. Here, RNA-seq was used to examine the gene expression profiles of Amphibalanus amphitrite cyprids in response to SIPC and to identify SIPC-activated intracellular signaling pathways. A total of 389 unigenes were differentially expressed in response to SIPC, and cement protein genes were not among them. KEGG enrichment analysis suggested that SNARE interactions in the vesicular transport pathway were significantly influenced by SIPC treatment, indicating a possible role for SIPC in triggering protein transportation and secretion. Several genes with specific functions in metamorphosis were found among the differentially expressed genes (DEGs). GO (Gene Ontology) enrichment analysis revealed that the DEGs were significantly enriched in enamel mineralization pathways, suggesting that SIPC may also be involved in the activation of mineralization. (C) 2020 Elsevier Inc. All rights reserved.