Aims: To acquire data on the safety-in-use of the probiotic Saccharomyces cerevisiae RC016 and test its ability to reduce genotoxicity caused by dietary aflatoxins (AFs). Methods and Results: The probiotic was orally administered to Wistar rats. Six groups (n = 6) were arranged: feed and probiotic controls, two levels of AFs-contaminated feed and two treatments including both the probiotic and the toxin. Genotoxiciy and cytotoxicity were evaluated with the bone marrow micronuclei assay and the comet assay and internal organs were macroscopically and microscopically examined. The tested S. cerevisiae strain did not cause genotoxicity or cytotoxicity in vivo, and it was able to attenuate AFs-caused genotoxicity. Saccharomyces cerevisiae RC016 did not cause any impairment on the rats' health and it showed no negative impact on the weight gain. Moreover, RC016 improved zootechnical parameters in AF-streated animals. The beneficial effects were likely to be caused by adsorption of AFs to the yeast cell wall in the intestine and the consequent reduction in the toxin's bioavailability. Conclusions: The dietary administration of RC016 does not induce genotoxicity or cytotoxicity to rats. Significance and Impact of the Study: Incorporation of RC016 in the formulation of feed additives increases animal productivity. Similar effects may even occur in human food applications.