Ganoderic acid A (GA‑A), a triterpenoid, has been demonstrated to suppress cell proliferation in various cancers, including breast cancer and osteosarcoma. However, its effect on human hepatocellular carcinoma (HCC) remains to be elucidated. The present study aimed to investigate the effect of GA‑A on HCC cells in vitro. The HepG2 and SMMC7721 human HCC cell lines were treated with differing concentrations of GA‑A for 24, 48 and 72 h. The cell growth rate, cell cycle and apoptosis, migration and invasion were determined using a Cell Counting Kit‑8, flow cytometry and transwell assays, respectively. The expression of apoptosis‑associated proteins was detected via western blot analysis. GA‑A significantly inhibited the proliferation of human HCC HepG2 and SMMC7721 cells in a dose‑dependent manner. Furthermore, GA‑A induced cell cycle arrest at the G0/G1 phase and apoptosis, and suppressed the migration and invasion of HCC cells. Furthermore, GA‑A decreased the expression of cyclin D1 and increased the expression of p21 and cleaved caspase‑3. In conclusion, GA‑A suppressed the proliferation of human HCC cells in vitro and may act as a promising natural therapeutic reagent in the treatment of HCC.