The present study aimed to investigate the potassium currents and further explore the role of potassium channels in drug response of gastric cancer cells. By patch-clamp technique, potassium currents of human gastric cancer cell SGC7901 were recorded in the mode of voltage clamp. Both 4-aminopyridine (4-AP) and tetraethylammonium (TEA) could almost completely block this current. The chemotherapeutic drugs, adriamycin or 5-fluorouracil could significantly increase the K(+) current density on SGC7901 cells in a dose-dependent manner. 4-AP or TEA was found to restrain adriamycin-induced apoptosis and enhance multidrug-resistant phenotype of SGC7901 cells. Up-regulation of Kv1.5, which has been found widely expressed in gastric cancer cells including SGC7901, increased the K(+) current density and sensitivity of SGC7901 cells to multiple chemotherapeutic drugs, whereas down-regulation of Kv1.5 enhanced the drug-resistant phenotype of SGC7901 cells. In conclusion, potassium channels may exert regulatory effects on multidrug resistance by regulating drug-induced apoptosis in gastric cancer cells.