C-type lectins have a variety of immunological functions in invertebrates. In order to investigate whether C-type lectin gene and carotenoids do have immune influences on noble scallop Chlamys nobilis under pathogen stress, acute challenges lasting 48 h to Vibrio parahaemolyticus, lipopolysaccharide (LPS), polyinosinic polycytidylic acid (Poly I: C), and PBS were conducted in noble scallop with different carotenoids content. A multi-CRD C-type lectin gene called Cnlec-1 was cloned and its transcripts under different challenges were determined. Full length cDNA of Cnlec-1 is 2267 bp with an open reading frame (ORF) of 1845 bp encoding 614 deduced amino acids, containing four carbohydrate recognition domains (CRD1, CRD2, CRD3 and CRD4). Phylogenetic tree analysis showed that CRDs of Cnlec-1 were clustered with CRDs of shellfish C-type lectins, especially closely related to Chlamys farreri and Argopecten irradians CRDs. Cnlec-1 transcripts were detected in hemocytes, mantle, gonad, kidney, intestines, gill and adductor. Compared with PBS control group, Cnlec-1 transcripts were up-regulated in V. parahaemolyticus, LPS and Poly I: C groups. Furthermore, Cnlec-1 transcript levels of Golden scallops were significantly higher than that of Brown ones at 3–48 h (P < 0.05) in V. parahemolyticus groups, at 24 h in LPS groups and at 12–24 h in Poly I: C groups. These results suggesting that Cnlec-1 is an important immune factor involved in the defense against pathogens in the noble scallop, and carotenoids can enhance the immunity of noble scallop through up-regulating Cnlec-1 to different immunostimulants.