Molecular analyses show that challenging fish with microcystin-LR (MC-LR) causes perturbations of microRNA (miRNA) signaling. However, the significance and scope of these alterations is currently unknown. To address this issue, we studied miRNA gene expression in the liver of whitefish, C. lavaretus, during 28 days of exposure to a subacute dose of MC-LR (100 ug*kg-1 body mass). Using the genome of Atlantic salmon (AGKD03), the mature miRNA library of Atlantic salmon (miRBase-21) and bioinformatics tools (sRNAbench), we discovered and annotated a total number of 377 distinct mature miRs belonging to 93 families of evolutionary conserved miRs, as well as 34 distinct novel mature miRNAs that were mapped to 14 distinct miRNA precursors. RNA-seq transcriptome profiling of liver tissues revealed differential miRNA expression in control and treated fish at 14 days (103 miRNAs were modulated) and at 28 days (114 miRNAs FDR<0.05 egdeR) of the treatment, subsequently validated by qPCR for ten selected differentially expressed miRNAs. Additional qPCR study confirmed the RNA-Seq data and revealed consistent, aberrant miRNAs expression profile in the later phase of MC-LR hepatotoxicity (7-28 d). Functional annotation analysis revealed that the aberrantly expressed miRs have target genes involved in cytoskeletal remodeling, cell metabolism, cell cycle regulation and apoptosis dysregulation of these processes in liver cells leads to cirrhosis and hepatocellular carcinoma in mammals. To enable deeper insight into the molecular responses of liver cells in fish exposed to MC-LR, we expanded the miRNome analysis by inclusion of miRNA variants (isomiRs) profiles, and we showed that the isomiR profiles of liver specific miR-122, and a few other miRNAs, correlated with MC-LR treatment. This finding may draw attention for future studies on a possible biological role of the miRNA variants in the toxin stressed liver. As more miRNA profiling studies with other toxins and other organisms are performed, it will be possible to obtain an miRNA connectivity grid highlighting miRNAs and their variants that drive the toxic effects in vertebrate liver.