As an important cold-water economic fish species, rainbow trout (Oncorhynchus mykiss) exhibits several intra-specific variation in skin pigmentation that can give rise to distinctive phenotypes, and wild-type rainbow trout with black skin (WR) and yellow mutant rainbow trout with yellow skin (YR) are the major two types in the farms, whose distinct skin colors make them suitable model for elucidating the skin pigmentation process. Skin color as a key indicator for selection in rainbow trout farming as well as has a strong visual impact on the consumer when rainbow trout are marketed. Previously, extensive studies have been conducted on skin color in rainbow trout, including the observation of skin spots and the expression analysis of some important pigment genes. However, up to date, no studies have systematically examined the molecular regulation mechanism of skin color difference between WR and YR through a high throughput method. Therefore, the aim of this study was to reveal the molecular regulation mechanism of skin color difference between these two strains at the mRNA and miRNA transcriptome level, and candidate genes, miRNAs and miRNA-mRNA pairs that may be responsible for rainbow trout albinism were obtained. Overall design: This study simultaneously analyzes mRNA and miRNA expression profiles and constructs miRNA-mRNA regulatory networks to identify key miRNA-mRNA pairs that may participate in skin color formation of WR and YR.