B‑cell translocation gene 2 (BTG2) is a tumor suppressor gene, which belongs to the anti‑proliferation gene family. Our previous study demonstrated that microRNA (miR)‑21 and the expression of BTG2 were negatively correlated during hepatocarcinogenesis. The aim of the present study was to investigate the effects of miR‑21 on the growth and progression of liver cancer cells, and to determine the underlying mechanism. A luciferase reporter assay was used to demonstrate that the BTG2 gene was a direct target of miR‑21. In addition, the effects of miR‑21 on cell growth and gene expression in HepG2 human hepatocellular carcinoma (HCC) cells were analyzed using reverse transcription‑quantitative polymerase chain reaction, western blotting, an MTT assay, flow cytometry, a Transwell invasion assay and a wound healing assay. The expression levels of miR‑21 in the HepG2 cells were significantly higher, compared with those in L02 normal liver cells. The expression levels of BTG2 in liver cancer cell lines (HepG2 and Huh7) were significantly lower, compared with that in the L02 cells. These results suggested that BTG2 was the direct target gene of miR‑21. The protein expression levels of BTG2 were inhibited by high expression levels of miR‑21, and increased by inhibition of the expression of miR‑21 in the HepG2 cells. Inhibition of miR‑21 reduced cell proliferation and invasion, and increased the rate of apoptosis in the HepG2 cells. These results indicated that miR‑21 regulates cell proliferation, invasion, migration and apoptosis in HepG2 cells, which may be associated with its effects on the expression of BTG2. The results of the present study may provide a basis for targeting the miR‑21/BTG2 interaction for the treatment of HCC.