In the present study, we investigated whether miRNA‑300 (miR‑300) is an oncogene in human liver cancer and sought to determine the mechanism underlying its activity. We also investigated the effect of miRNA‑300 on the growth in liver cancer. To identify its target molecule, we performed luciferase assays. The downstream signaling pathway was detected by immunohistochemical (IHC) analysis in human HCC tissues, and the protein levels of AKT, 4E‑BP1, S6K1, SNAIL and MMP2 were determined using western blotting. miR‑300 levels were higher in patients with high‑stage HCC, and miR‑300 promoted cell growth both in vitro and in vivo. miRNA‑300 inhibited the luciferase activity of FOXO1 by targeting its 3'‑untranslated region (UTR), and overexpression of miR‑300 upregulated the protein levels of phospho‑AKT, phospho‑4E‑BP1, phospho‑S6K1, SNAIL and MMP2. These data revealed that miRNA‑300 functions as an oncogene in liver cancer by inhibiting FOXO1 and interacting with the AKT/mTOR signaling pathway.