The cation-dependent mannose-6-phosphate receptor (CD-MPR) is a member of the P-type lectin family. As a type I transmembrane glycoprotein, it functions in the delivery of newly synthesized acid hydrolases from the trans-Golgi network to endosomes for their subsequent transfer to the lysosome by binding the mannose-6-phosphate receptor-recognition moieties in the hydrolases. However, the functions of CD-MPR in immune responses are seldom reported. In the present study, we identified a CD-MPR-like molecule in Marsupenaeus japonicus and designed it as MjCD-MPR. It was significantly upregulated after challenge with Vibrio anguillarum at the mRNA and protein levels. Knockdown of MjCD-MPR resulted in a significant increase in the amount of V. anguillarum in the hemolymph of shrimp, which suggested that MjCD-MPR plays a role in shrimp antibacterial defense. The recombinant extracytoplasmic region of MjCD-MPR could bind gram-positive and gram-negative bacteria by interaction with peptidoglycan, lipopolysaccharide, and lipoteichoic acid. MjCD-MPR showed no direct bacteriostatic or bacteriocidal activity. Knockdown of MjCD-MPR decreased the expression levels of several antimicrobial peptides (Alf-C1, Alf-E1, Crustin I-2, and Crustin I-3), suggesting that MjCD-MPR promotes the expression of antimicrobial peptides in shrimp. In summary, working as a pattern recognition receptor, MjCD-MPR recognizes invading bacteria and triggers the expression of AMPs against bacterial infection in shrimp.