To understand the regulation of genetic damage by epigenetics at the early stage of carcinogenesis after hexavalent chromium (Cr(VI)) and assessed genetic damage to explore their association with DNA repair genes mediated by differently expressed miRNA. Genetic damages were evaluated using cytokinesis-block micronucleus assay (CBMN) and serum 8-hydroxyguanine (8-OHdG) ELISA assay. Blood Cr level showed significant association with plasma miR-3940-5p level (r=-0.33, P=0.001) and non-linear relationship with micronuclei frequency in CBMN and serum 8-OHdG level (β(std)=0.29, P=0.039; β(std)=0.35, P=0.001), with micronuclei frequency not increasing apparently under high Cr exposure. In contrast, no significant association was found between plasma miR-3940-5p level and the two genetic indicators. However, plasma miR-3940-5p level was linked to micronuclei frequency under high blood Cr level (β(std)=0.18, P=0.015). To explore the effect of miR-3940-5p on genetic damage under high Cr exposure, the protein expression levels of miR-3940-5p-mediated DNA repair genes in leukocytes were quantified using enzyme-linked immunosorbent assay for subjects with high blood Cr level. The results showed that XRCC2 and BRCC3 protein levels were statistically associated with miR-3940-5p level respectively (β(std)=-0.31, P=0.010; β(std)=-0.24, P=0.037). Meanwhile, a weak but statistically negative association between XRCC2 level and micronuclei frequency was found (β(std)=-0.15, P=0.027). These data suggests that high Cr(VI) does not always aggravate genetic damage after reaching a high Cr(VI) exposure in real situation, which may be due to the regulation of miRNA on DNA repair genes responsive to high Cr(VI) exposure.