Class B scavenger receptors (SRBs) have been well-studied in bacteria-induced immune responses in invertebrates. However, the status of SRB-defending viruses remains unclear. In this study, we identified a scavenger receptor in Procambarus clarkii (crayfish), which is homologous to mammalian SRBs, and designated it as PcSRB. The expression of PcSRB was upregulated after the WSSV challenge. The survival rate of crayfish was decreased, but the WSSV copy number increased after PcSRB knockdown during virus invasion. In addition, PcSRB bound to WSSV. Furthermore, we detected how PcSRB interacted with WSSV, and we found that PcSRB could bind to cholesta-3,5-diene, (CD3,5), a novel WSSV lipid ligand, rather than dibutyl phthalate (DBP). Besides, PcSRB could bind to VP19, VP26, and VP28, rather than VP24. Mutant-binding experiments demonstrated that the hydrophobic domain (130-180 aa) of PcSRB is important for recognizing WSSV. Furthermore, PcSRB might promote lysosomal eliminating function to degrade WSSV. Altogether, we identified a new mechanism for scavenger receptor recognition and resistance to WSSV.IMPORTANCEPcSRB could bind to WSSV directly. PcSRB could interact with WSSV via binding to lipid molecule CD3,5 and viral envelope proteins. PcSRB could influence lysosomal activation.