AIM: To investigate the role of chloride channels in the apoptosis of human poorly differentiated nasopharyngeal carcinoma CNE-2Z cells induced by arsenic trioxide (As2O3).METHODS: The apoptotic rates of CNE-2Z cells induced by As2O3 for 24 h or 48 h were monitored by flow cytometry.The technique of whole-cell patch clamp was used to record the currents activated by As2O3 in the CNE-2Z cells.The inhibition of As2O3-induced apoptosis by chloride channel blocker DIDS in the CNE-2Z cells was analyzed by flow cytometry.RESULTS: As2O3 at 5 μmol/L induced apoptosis of CNE-2Z cells in time-dependent manner.The currents with outward rectification were activated when the cells were exposed to 5 μmol/L As2O3.No obvious time-and voltage-dependent inactivation of the currents was observed.The reverse potential of the currents was close to the equilibrium potential for chloride.The activated currents were inhibited by the chloride channel blockers NPPB and DIDS.The 47% hypertonic solution inhibited the activated currents completely.Chloride channel blocker DIDS inhibited the apoptosis of CNE-2Z cells induced by As2O3.CONCLUSION: As2O3 activates volume-sensitive chloride channels, and chloride channels may play an important role in the apoptosis of CNE-2Z cells induced by As2O3.