Leucine-rich repeat (LRR) is a structural motif has important recognition function in immune receptors, such as Tolls and NOD-like receptors (NLRs). The immune-related LRR proteins can be divided into two categories, LRR-containing proteins and LRR-only proteins. The latter contain LRR motifs while they are without other functional domains. However, the functional mechanisms of the LRR-only proteins were still unclear in invertebrates. Here, we identified a gene encoding a secretory LRR-only protein, which possessed similarity with vertebrate CD14 and was designated asLvCD14L, from the Pacific whiteleg shrimpLitopenaeus vannamei. Its transcripts in shrimp hemocytes were apparently responsive to the infection ofVibrio parahaemolyticus. Knockdown ofLvCD14Lwith dsRNA resulted in significant increase of the viable bacteria in the hepatopancreas of shrimp uponV. parahaemolyticusinfection. Further functional studies revealed that LvCD14L could bind to microorganisms’ PAMPs, showed interaction with LvToll1 and LvToll2, and regulated the expression ofLvDorsalandLvALF2in hemocytes. These results suggest that LvCD14L functions as a pattern recognition receptor and activates the NF-κB pathway through interaction with LvTolls. The present study reveals a shrimp LvCD14L-Tolls-NF-κB signaling pathway like the CD14/TLR4/NF-κB signaling pathway in mammalians, which enriches the functional mechanism of secretory LRR-only immune receptors during pathogens infection in invertebrates.