This meta-analysis aimed to investigate the effects of beta-carotene supplements alone on cancer prevention as reported by randomized controlled trials (RCTs). We searched PubMed, EMBASE, and CENTRAL. Among the 848 articles searched, 6 randomized controlled trials, including 40,544 total participants, 20,290 in beta-carotene supplement groups, and 20,254 in placebo groups, were included in the final analysis. In a meta-analysis of 6 RCTs, beta-carotene supplements had no preventive effect on either cancer incidence [relative risk (RR) = 1.08, 95% confidence interval (CI) = 0.99-1.18] or cancer mortality (RR = 1.00, 95% CI = 0.87-1.15). Similar findings were observed in both primary prevention trials and secondary prevention trials. Subgroup analyses by various factors revealed no preventive effect of beta-carotene supplementation on cancer prevention and that it significantly increased the risk of urothelial cancer, especially bladder cancer (RR = 1.52, 95% CI = 1.03-2.24) and marginally increased the risk of cancer among current smokers (RR = 1.07, 95% CI = 0.99-1.17). The current meta-analysis of RCTs indicated that there is no clinical evidence to support the overall primary or secondary preventive effect of beta-carotene supplements on cancer. The potential effects, either beneficial or harmful, of beta-carotene supplementation on cancer should not be overemphasized.