Complement 1q-binding protein (gC1qR), a multi-functional cellular protein, is able to bind the globular head region of C1q molecule (gC1q), playing an important role in regulation of immune response and host defense against bacterial infection. In this study, the full length of a gC1qR ortholog (OngC1qR) was identified and characterized from Nile tilapia (Oreochromis niloticus). The cDNA of OngC1qR ORFs consisted of 870 bp of nucleotide sequence encoding a 289 amino acid residue polypeptide. The deduced amino acid sequence is highly homologous to teleost, containing a MAM33p domain, two potential glycosylation sites, and a putative cell adhesion site EGD (Glu-Gly-Asp). Spatial mRNA expression analysis revealed that the OngC1qR was expressed ubiquitously in all examined tissues, with a high expression in the liver. The OngC1qR expression was significantly up-regulated in liver, spleen and head kidney following in vivo challenges with Streptococcus agalactiae. A high up-regulation was also detected in head kidney leukocytes in vitro stimulation with Streptococcus agalactiae. In addition, immunofluorescence detection illustrated that the OngC1qR was located at the cell surface of leukocytes. Recombinant OngC1qR protein was able to not only bind LPS, LTA, S. agalactiae and Aeromonas hydrophila, but also possess binding capability with the ligand OnC1qs. Taken together, the results indicated that OngC1qR might be involved in host defense against bacterial infection in Nile tilapia. •Full-length cDNA of gC1qR was identified and characterized in Nile tilapia.•Expressions of OnC1qR were significantly up-regulated upon LPS and bacterial challenges.•OnC1qR was located on the surface of leukocytes.•Recombinant OnC1qR was able to bind bacteria and ligand OnC1qs.