The comparative transcriptomic analysis was performed on natural and albino blue discus with white discus fish (Symphysodon haraldi) respectively to excavate genes related to iridophores in blue skin. It was found a total of 2, 192 different expression genes (DEGs) in natural blue fish, including 1, 270 up-regulated and 922 down-regulated genes. The DEGs were primarily enriched in purine nucleotide biosynthetic process, actomyosin structure organization, purine-containing compound biosynthetic process, oxidative phosphorylation, citrate cycle and other functions. For the albino blue discus fish compared to white one, there were 1, 859 up-regulated and 1, 309 down-regulated DEGs. Similarly, the dominant enriched pathways of these genes were oxidative phosphorylation, ribonucleoside diphosphate metabolic process, ADP metabolic process, cation binding, glycine, serine and threonine metabolism and other functions. In order to further explore candidate genes participating in iridophores appearing color, by comparing the database, a total of 32 and 38 DEGs were screened out in natural blue and albino blue discus, respectively. It could be predicted that alkal2b, gpnmb, fhl2 and pka were associated with the development of iridophores, and pgam, prtfdc1, pnp, slc23a1, slc2a9, rab38, rdh10, psat1, and paics might attend guanine synthesis and transportation in iridophores. This study might ground for in-depth analysis of the formation and regulation mechanism of blue structural color in fish.