Coproporphyrinogen-Ⅲ oxidase (CPOX) is a key enzyme in the synthesis of porphyrins, which plays an important role in the formation of pigment. cDNA of Meretrix meretrix CPOX (MmCPOX) was cloned by SMART RACE techniques, then the bioinformatics and expression profiles in different tissues and developmental stages were analyzed. The results indicated that the full length cDNA of MmCPOX gene was 1490 bp, containing a 1173 bp opening reading fame(ORF) encoding 390 amino acids. The molecular weight of MmCPOX was 12.04 ku and pI was 5.05. It was also predicted that protein MmCPOX had a transmembrance region and a Coprogen-oxidas region. Comparisons of amino acid sequence, MmCPOX was highly homologous with Aplysia californica and shares 64.5% similarity. The result of qRT-PCR showed that MmCPOX gene was expressed in all stages, and significantly increased from D-shaped larva stage (P<0.01). MmCPOX was expressed in all seven tissues, in which the expressions in mantle and blood were significantly higher than those of other tissues (P<0.01), indicating that it was related to synthesis of hematoporphyrin and formation of shell porphyrin. Considering different shell colors, the relative expressions of mantle in red color, dark fringe and thin checkered shells, were significantly different from the black and white shells (P<0.05), suggesting that MmCPOX gene was responsible for the formation of red and brown shell color.