Abstract: Objective: To investigate the anti-tumor effects of Arsenic Trioxide(As ₂O₃) on human hepatocellular car-cinoma cell line HepG₂ and to explore the underlying mechanism. Methods: MTT assay was used to observe the inhibitoryactions of As₂O₃ on HepG₂ cells at various concentrations. The apoptotic rate of the cells was detected by flow cytometry.The expression of p-MEK4, JNK, p-JNK, Caspase-3 and PARP was detected by Western blot. Results: The growth of theHepG₂ cell line was remarkably inhibited by As ₂O₃ in vitro, and significant apoptosis was present. As₂O₃ induced activationof Caspase-3 and PARP cleavage. Before apoptosis was seen, activation of JNK was detectable 10 min after the cells weretreated with As₂O₃. As a JNK inhibitor, SP600125 partly suppressed As ₂O₃ -induced activation of Caspase-3 and PARPcleavage. Conclusion: As ₂O₃ can inhibit the proliferation of human hepatocellular carcinoma cell line HepG₂ and induceapoptosis. The JNK signaling pathway is involved in the mechanism of As₂O₃ -induced apoptosis.