Be absent of adaptive immunity which have both specificity and memory, invertebrates seem to have evolved alternative adaptive immune strategies to resist various intruding pathogens. Whereas vertebrates could generate a wide range of immunological receptors with somatic rearrangement, invertebrates possibly depend on alternative splicing of pattern-recognition receptors (PRRs). Recently, it has been suggested that a member of the immunoglobulin superfamily (IgSF), Down syndrome cell adhesion molecule (Dscam), plays a crucial role in the alternative adaptive immune system of invertebrates. At present, we successfully isolated and characterized the first crab Dscam from Eriocheir sinensis. EsDscam has typical domain architecture compared with other Dscam orthologs, including one signal-peptide, 10 immunoglobulin (Ig) domains, 6 fibronectin type III domains (FNIII), one transmembrane domain (TM) and one cytoplasmic tail. We had detected four hypervariable regions of EsDscam in the N-terminal halves of Ig2 (25) and Ig3 domain (30), the complete Ig7 (18) and also the transmembrane domain (2), potentially generate 27,000 unique isoforms at least. Transcription of EsDscam were both a) detected in all tissues, especially in immune system, digestive system and nerve system; b) significantly induced in hemocytes post lipopolysaccharides (LPS), peptidoglycans (PG) and β-1, 3-glucans (Glu) injection. Importantly, we had detected membrane-bound and secreted Dscam isoforms in E. sinensis, and showed that secreted isoforms were extensively transcribed post different PAMPs challenge respectively. Results from immuno-localization assay revealed that EsDscam evenly distributed in the cell surface of hemocytes. These findings indicated that EsDscam is a hypervariable PRR in the innate immune system of the E. sinensis.