This meta-analysis aimed to investigate the preventive effect of selenium supplements alone on cancer as reported by randomized controlled trials (RCTs). We searched PubMed, EMBASE, and the Cochrane Library in July 2009. Of the 461 articles searched, 8 articles on 9 RCTs, which included 152,538 total participants, 32,110 in antioxidant supplement groups, and 120,428 in placebo groups, were included. In a random-effects meta-analysis of all 9 RCTs, selenium supplementation alone was found to have an overall preventive effect on cancer incidence [relative risk (RR) = 0.76; 95% confidence interval (CI) = 0.58-0.99]. Among subgroup meta-analyses, the preventive effect of selenium supplementation alone on cancer was apparently observed in populations with a low baseline serum selenium level (<125.6 ng/mL) (RR = 0.64; 95% CI = 0.53 to 0.78; I(2) = 45.5%; n = 7) and in high-risk populations for cancer (RR = 0.68; 95% CI = 0.58 to 0.80; I(2) = 41.5%; n = 8). The meta-analysis of randomized controlled trials indicates that there is possible evidence to support the use of selenium supplements alone for cancer prevention in the low baseline serum selenium level population and in the high-risk population for cancer.