Abstract Microcystin-LR (MCLR) is a widespread cyanotoxin, which can influence genes transcription and cause nucleic acid damage in different organisms. To identify MCLR induced transcriptionally changed hepatic genes in bighead carp by subtractive suppression hybridization, we obtained the cDNA fragment of cda. Then we cloned its full-length cDNA, which encodes a cytidine deaminase (CDA). 3D structure prediction showed that the 3D structure and amino acid residues related to function sites of bighead carp CDA were highly conserved. Bighead carp CDA shared high identities with other CDA sequences, and evolved closely to non-mammalian CDAs. Bighead carp expressed cda in all tested tissues under normal situation, and changed its expression profile in a time inversely dependent and dose dependent manner to MCLR, so as to protect itself from MCLR induced toxic damage. These indicated that cda might be involved in anti-MCLR response, especially in the regulation of cytidine and dexocytidine metabolism pathway.