The serine protease with clip domain is a new serine protease family and plays an important role in innate immunity. One EST sequence with high homology with serine protease gene of other species was found from the cDNA library of Sinonovacula constricta and then the complete ORF and 3′-UTR sequence were obtained by PCR. The 5′-UTR sequence was got by 5′-RACE. The cDNA of this gene was 1 228 bp, which consists of a 66 bp 5′-untranslated region (UTR)，a 1 002 bp open reading frame (ORF) and a 160 bp 3′-UTR. The translated protein is composed of 333 amino acids containing a signal peptide. Sequence analysis of the protein revealed that the protein contained a clip domain and a Tryp_SPc domain. The three disulfide bonds were formed by six conserved cysteines in the clip domain and the catalytic triad (HDS) was contained in the Tyrp_SPc domain.This gene was designated as ScSP. The quantitative reverse transcriptase (qRT-PCR) analyses showed that the ScSP can be expressed in six tissues. The expression level of ScSP gene was highest in liver, then in gonad, but lowest in water pipe, mantle and gill. The expression of ScSP gene in liver tissue was up regulated at 4h and 8h following the challenge with Vibrio anguillarum. These results indicated that ScSP is a new serine protease with clip domain and might be involved in innate immunity, which contributes to understanding the structure and function of serine protease in the future.