We used MTT to analyze cell proliferation activity and noted that there was a considerable decrease of miR‑503 in HCC tissues and cell lines when measured against the controls. miR‑503 upregulation decreased expression of eukaryotic translation initiation factor 4E (EIF4E), and reduced HCC cell proliferation and sensitized HCC cells to anticancer drugs. miR‑503 overexpression hindered luciferase activity of EIF4E 3' untranslated region-based reporter construct among HepG2, BEL-7402, and SMMC-7721 cells, revealing that miR‑503 may increase sensitivity to therapies at least partially through targeting EIF4E suppression of HCC proliferation.