Objective To investigate the potential role of the pore-formation in the hemolytic activity of tentacle-only extract (TOE) from the jellyfish Cyanea capillata. Methods The effects of various cations, including K+, Ca2+, Mg2+, Mn2+, Zn2+, Cu2+, Fe2+ , La3+and NH4+ on the hemolytic activity of TOE were compared in two different test systems: 1% whole blood and 0.45% erythrocyte suspension with the same erythrocyte concentration. Results The hemolytic activities of TOE in both tests were inhibited by Mn2+, Zn2+, La3+, Cu2+ and Fe2+, and were promoted to a minor extent by K+, Ca2+, Mg2+ and NH4+. The chelating agent EDTA also inhibited the hemolytic activity of TOE. Conclusion The pore-formation mechanism might play an important role in the hemolytic activity of TOE.