Grass carp hemorrhagic disease is a fatal disease caused by the grass carp reovirus (GCRV). The aberrant regulation of transcripts has been implicated in many types of diseases. In the present study, we characterized mRNA and miRNA transcriptomes of different virulent GCRVs using RNA sequencing (RNA-Seq). One hundred eighteen miRNAs were identified as being differentially expressed between different virulent viruses in grass carp fibroblasts. Eight miRNAs were selected to verify the RNA-Seq results using RT-PCR and mRNA methods. In total, 996 differentially expressed mRNA genes were identified in grass carp fibroblasts, while 901 miRNA-mRNA target pairs were observed to be inversely regulated in grass carp fibroblasts. Integrated mRNA/miRNA expression profiling analysis results showed that the most influenced processes were the immune response and cell death. Three miRNAs were shown to exhibit the same expression patterns when two different methods were used and had important functions during viral infection. These results provide insights into the miRNA-mediated regulation of mRNA and valuable resources on transcript variation and regulation during GCRV infection, which are potentially useful for mechanistic and drug studies.