OBJECTIVE: To study the changes of telomerase activity and protein expression of phosphorylated (activated) extracellular regulated protein kinases (ERK1 and ERK2) in the course of inhibiting hepatocarcinomatous cell proliferation and inducing cell apoptosis by three kinds of chemotherapy drugs: Harringtonine (HRT), Vincristine (VCR), and Etoposide (Vp16). To discuss the regulative function to hepatocarcinomatous cell apoptosis and interrelation of telomerase and ERK. METHODS: Cytotoxicity assay, flow cytometry analysis, telomerase repeat amplification protocol assay (TRAP), bioluminescence analysis, and western blot were used in this experiment. RESULTS: HRT, VCR, and Vp16 could inhibit cell proliferation (0.28% 0.08%, 0.25% 0.16%, 0.24% 0.11%), induce apoptosis (21.12%, 28.83%, 12.30%), inhibit telomerase activity, and down-regulate the protein expression of phosphorylated ERK. CONCLUSIONS: It might be through ERK signal transduction pathways that chemotherapy drugs down-regulate telomerase activity and induce apoptosis.