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A randomized, double-blind, placebo controlled clinical trial was conducted in arsenic exposed population in Inner Mongolia to know the efficacy of folic acid supplementation on arsenic-inducted DNA d o xidative damage. Methods: In this randomized clinical trial （RCT）, a total of 450 participants were enrolled and randomly assigned to 3 groups to receive folic acid （FA） 0.4mg/day （Low FA）, 0.8mg/day （High-FA） or placebo （Control） for 8 weeks. The urine 8-hydroxy-2'-deoxyguanosine（8-OHdG） and creatinine （Cr） concentration at pre- and post-FAS were measured with enzyme-linked immunosorbent assay （ELISA） kit and high-performance liquid chromatography （HPLC）, respectively. A multivariate general linear model （GLM） was applied to assess the individual effects of FA and the joint effects between FA and hypercholesterolemia on oxidative damage improvements. This clinical trial was registered with ClinicalTrials.gov, number NCT02235948. Results: Compared with placebo, after adjusted for some potential confounding factors, the urinary 8-OHdG/Cr concentration significantly decreased after 56 days FAS in a dose-response fashion（P<0.001）. A joint effect between hypercholesterolemia and FAS on urinary 8-OHdG/Cr reduction was also observed （P=0.001）. Conclusions: The present study demonstrates that FAS is beneficial for DNA oxidative damage repair. People with hypercholesterolemia might have better effects on the improvement of DNA lesion.