Eutrophication can induce hypoxia/anoxia and rich organic matter at the sediment-water interface in surface waters. When eutrophic waters are impacted with mercury (Hg) pollution, methylmercury (MeHg) production ability (MPA) of surface sediment would increase and more MeHg might be produced. To tackle this risk, this study firstly collected samples of surface sediment and overlying water from a typical eutrophic lake-Taihu Lake. Then from a sediment-water simulation system, we demonstrated that eutrophic waters were able to methylate Hg spontaneously, and that sediment is the major Hg sink in the system. After the addition of HgCl2 solution (approximately 1 mg L −1 in the slurry), MeHg concentrations in the sediment increased by 11.7 times after 48 h. The subsequent column experiments proved that O2 nanobubbles could significantly decrease the MPA of surface sediment, by up to 48%. Furthermore, we found that O2 nanobubbles could remediate anoxia mainly by increasing dissolved oxygen (from 0 to 2.1 mg L −1), oxidation-reduction potentials (by 37% on average), and sulfate (by 31% on average) in the overlying water. In addition, O2 nanobubbles could also help decrease organic matter concentration, as was revealed by the decline of dissolved organic carbon in the overlying water (by up to 57%) and total organic carbon in surface sediment (by up to 37%). The remediation of anoxia and reduction of organic matter could contribute to the decrease of hgcA gene abundance (by up to 86%), and thus result in the reduction of MPA after the addition of O2 nanobubbles. This study revealed the risk of MeHg production in case Hg pollution occurs in eutrophic waters and proposed a feasible solution for MeHg remediation.