AIM: To examine the effect of insulin on the proliferation of human hepatocellular carcinoma cell and its possible mechanisms. METHODS: The human hepatocellular carcinoma cell line(HepG-2) was used to study the changes in calcium ion across plasma membrane (Ca 2+ APM)under the action of insulin by the assay of atomic absorption spectrum, and in the proliferation under the action of insulin and calcium ion antagonist (isoptin). RESULTS: The influx of Ca 2+ APM and the proliferation was increased after insulin administration, but the proliferation was inhibited by isoptin. CONCLUSION: Changes in the homeostasis of calcium ion across plasma membrane was involved in the effect of insulin on the proliferation of human hepatocellular carcinoma.