MicroRNAs (miRNAs) are small, non‑coding RNAs that inhibit the expression of target protein coding genes at the post‑transcriptional level. miR‑122 is a liver specific miRNA. Notably, miR‑122 is used by the hepatitis C virus (HCV) for triggering viral replication by interacting with the 5' untranslated region of the HCV RNA. The present study demonstrated that miR‑122 inhibited the expression of signal transducer and activator of transcription 3 (STAT3), an antivirus response repressor. The HCV RNA acted as an 'miRNA sponge', which upregulated the expression of STAT3 by sealing miR‑122. Subsequently, it was confirmed that this miR‑122 sponge function of HCV RNA repressed the expression of polyinosinic‑polycytidylic acid‑stimulated type I interferons. The present study provided a deeper understanding of the complex role of miR‑122 in the progression of HCV infection and supported the miR‑122 inhibition strategy in anti‑HCV infection treatment.