This study aimed to improve our understanding of the mechanisms of liver regeneration in sharks and to identify the microRNAs that participate in liver regeneration and other liver-related diseases. To this end, normal and regenerating liver tissues from C. plagiosum were harvested 0, 3, 6, 12 and 24 h after partial hepatectomy (PH) and were sequenced using the Illumina/Solexa platform. In total, 309 known microRNAs and 590 novel microRNAs were identified in C. plagiosum. There were 368 microRNAs differentially expressed between the normal and regenerating livers. Using target prediction and GO analysis, most of the differentially expressed microRNAs were assigned to functional categories that may be involved in regulating liver regeneration, such as cell proliferation, differentiation and apoptosis. Additionally, this study adds several novel microRNAs to the database, which will help identify microRNAs in other genetically related species and provides a starting point for future studies aimed at understanding the roles of microRNAs in liver regeneration and other liver diseases. Overall design: Sample 1 is the normal C. plagiosum liver, sample 2, sample 3, sample 4 and sample 5 is the regenerating liver obtained 3, 6, 12 and 24 h after PH, respectively.