Ion channels are involved in normal physiologic processes and in the pathology of various diseases. In this study, we investigated the presence and potential function of transient receptor potential melastatin 7 (TRPM7) like channels in the survival of AGS cells, human gastric adenocalcinoma cells, using a combination of patch-clamp recording, RT-PCR, western blotting, small interfering RNA (siRNA), and MTT (thiazolyl blue tetrazolium bromide) assay. AGS cells have been found to express endogenously TRPM7 like current. This current can be inhibited by La3+, 2-aminoethoxydiphenyl borate (2-APB), or intracellular Mg2+, consistent with the TRPM7 current being activated. Reverse transcription-PCR and western blotting detected the expression of TRPM7 mRNA and protein in these cells. Transfection of AGS cells with TRPM7 siRNA significantly reduced the expression of TRPM7 protein and TRPM7 like current. Furthermore, we found that TRPM7 like current is critical for the survival of AGS cells. Blockade of TRPM7 like channels by La3+ and 2-APB or suppression of TRPM7 expression by siRNA inhibited the survival of these cells. In summary, AGS cell lines express the nonselective cation channel TRPM7 whose presence is essential for cell survival.