Catfish (Pangasianodon hypophthalmus) is one of the most commonly farmed catfish species in the Mekong Delta. Both domestically and internationally, people are increasingly consuming catfish due to their high nutritional value. To enhance competitiveness, we need to focus on developing and improving the quality and quantity of catfish. In recent years, the production and consumption of catfish have faced numerous challenges, including unstable prices and fish diseases, particularly the high mortality rate (50–90%) due to liver, kidney, and hemorrhagic diseases. The use of antibiotics in disease treatment leads to antibiotic residues in fish meat and drug resistance. Vaccines for fish still have many limitations in distribution and preservation. As a result, we aimed to develop a new biological product capable of preventing liver, kidney, and hemorrhagic disease in fish, as well as bacterial diseases in fish in general. Only fish harbors the Toll-like receptor (TLR) 22 receptor, which recognizes and binds to viral dsRNA and lipopolysaccharides through leucine-rich repeat sequences (LRR), which can be exploited to capture bacteria. In this study, we produced the TLR22 receptor as a recombinant protein and evaluated its interaction with bacteria. We constructed the plasmid pET22b-tlr22 in E. coli MC1061, expressed the TLR22 receptor in E. coli SHuffle® T7 Express, and confirmed it by Western blot using anti-His-tag (6xHis) antibodies. The Dot-blot technique assessed the bacterial binding ability. Results showed that the TLR22 receptor could bind to Gram-positive bacteria. This study is a foundation for further research on developing biological products to supplement fish feed for treating bacterial diseases in catfish, and other fish species.