microRNA (miRNA) dysfunction is believed to play important roles in human diseases, including viral infectious diseases. Hepatitis C virus (HCV) infection promotes the development of steatosis, cirrhosis and hepatocellular carcinoma, which is genotype-specific. In order to characterize the miRNA expression profile of Huh-7 cells expressing the HCV core 3a vs. 1b, microarrays and real-time PCR were performed. Consequently, 16 miRNAs (5 miRNAs upregulated and 11 miRNAs downregulated) were found to be dysregulated. In addition, we generated the predicted and validated targets of the differentially expressed miRNAs and explored potential downstream function categories and pathways of target genes using databases of Gene Ontology (GO) and PANTHER and the database for annotation, visualization and integrated discovery (David). The computational results indicated that the dysregulated miRNAs might perform the functions of cellular metabolism and cellular growth. Finally, these biological effects were preliminarily validated. This study identifies a specific miRNA expression profile in cells expressing HCV core proteins of different genotypes (genotype 3a and 1b), which may account for the variable pathophysiological manifestation associated with HCV infection.