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Methylmercury (MeHg) is a highly poisonous form of mercury and a risk factor for kidney impairment in humans that currently has no effective means of therapy. Ferroptosis is a non‐apoptotic metabolic cell death linked to numerous diseases. It is currently unknown whether ferroptosis takes part in MeHg‐induced kidney damage. Here, we established a model of acute kidney injury (AKI) in mice by gavage with different doses of MeHg (0, 40, 80, 160 μmol/kg). Serological analysis revealed elevated levels of UA, UREA, and CREA; H&E staining showed variable degrees of renal tubule injury; qRT‐PCR detection displayed increased expression of KIM‐1 and NGAL in the groups with MeHg treatment, indicated that MeHg successfully induced AKI. Furthermore, MDA levels enhanced in renal tissues of mice with MeHg exposure whereas GSH levels decreased; ACSL4 and PTGS2 nucleic acid levels elevated while SLC7A11 levels reduced; transmission electron microscopy illustrated that the density of the mitochondrial membrane thickened and the ridge reduced considerably; protein levels for 4HNE and TfR1 improved since GPX4 levels declined, all these results implying the involvement of ferroptosis as a result of MeHg exposure. Additionally, the observed elevation in the protein levels of NLRP3, p‐p65, p‐p38, p‐ERK1/2, and KEAP1 in tandem with downregulated Nrf2 expression levels indicate the involvement of the NF‐κB/NLRP3/MAPK/Nrf2 pathways. All the above findings suggested that ferroptosis and the NF‐κB/NLRP3/MAPK/Nrf2 pathways are implicated in MeHg‐induced AKI, thereby providing a theoretical foundation and reference for future investigations into the prevention and treatment of MeHg‐induced kidney injury.