Hepatocellular carcinoma has the highest prevalence with poor prognosis in liver cancers. Effective treatment strategies are urgently needed to improve the survival of patients with hepatocellular carcinoma. Strychnine, the major active ingredient of the seed of Strychnos nux-vomica L., has been reported to possess an anti-hepatocellular carcinoma function while the underlying mechanism is not fully understood. Here we aim to explore strychnine's effect on the proliferation and apoptosis of human hepatoma HepG2 cells and clarify mechanism. The cytotoxic activity of strychnine against HepG2 cells was measured. Flow cytometry was used to assess cell apoptosis. The miR-122 expression level was measured via real time quantitative PCR IP 2038 10920 On: Sun 18 Jun 2023 10:22:18 and cyclin G1 and anti-apoptoticCopyrghproteins : includingAmerican surScientvivin icand P livinblisherswere assessed using Western blot. Strychnine decreased the viability of hepatocelulacarcinoma cells and induced their apoptosis in vitro. The Deliver ed by Ingenta levels of livin and survivin were decreased in HepG2 cells after strychnine treatment. By restraining cyclin G1 expression in HepG2 cells, strychnine upregulated liver-specific miR-122 level for the induction of apoptosis. Therefore, strychnine possessed the ability to inhibit cell proliferation and induce apoptosis. Strychnine may be applied for treating liver cancer.