The objective of this study was to explore whether magnesium levels (Mg) in drinking water modify the effects of nitrate on colon cancer risk. A matched case-control study was used to investigate the relationship between the risk of death from colon cancer and exposure to nitrate in drinking water in Taiwan. All colon cancer deaths of Taiwan residents from 2003 through 2007 were obtained from the Bureau of Vital Statistics of the Taiwan Provincial Department of Health. Controls were deaths from other causes and were pair-matched to the cases by gender, year-of-birth, and year-of-death. Information on the levels of nitrate-nitrogen (NO(3)-N) and Mg in drinking water were collected from Taiwan Water Supply Corporation (TWSC). The municipality of residence for cases and controls was assumed to be the source of the subject's NO(3)-N and Mg exposure via drinking water. The results of our study show that there is a significant trend towards an elevated risk of death from colon cancer with increasing nitrate levels in drinking water. Furthermore, we observed evidence of an interaction between drinking water NO(3)-N and Mg intake via drinking water. This is the first study to report effect modification by Mg intake from drinking water on the association between NO(3)-N exposure and colon cancer risk.