Having multidisciplinary applications, iron oxide nanoparticles can inevitably enter aquatic system and impact inhabitants such as fish. However, the studies in this context have ignored the significance of obvious interaction of iron oxide nanoparticles with other persistent co-contaminants such as mercury (Hg) in the modulation of the toxicity and underlying mechanisms of iron oxide nanoparticles and Hg alone, and concomitant exposures. This study aimed to evaluate lipid peroxidation (LPO) and its control with glutathione (GSH) and associated enzymes (such as glutathione reductase, GR; glutathione peroxidase, GPX; glutathione sulfo-transferase, GST) in European eel (Anguilla anguilla L.) hepatocytes exposed to stressors with following schemes: (i) no silica-coated iron oxide nanoparticles functionalized with dithiocarbamate (Fe3O4@SiO2/Si DTC, hereafter called 'FeNPs'; size range 82 ± 21 to 100 ± 30 nm) or Hg, (ii) FeNPs (2.5 μg L(-1)) alone, (iii) Hg (50 μg L(-1)) alone and (iv) FeNPs + Hg concomitant condition during 0 to 72 h. The exhibition of a differential coordination between GSH regeneration (determined as GR activity) and GSH metabolism (determined as the activity of GPX and GST) was perceptible in A. anguilla hepatocytes in order to control FeNPs, Hg and FeNPs + Hg exposure condition-mediated LPO. This study revealed the significance of a fine tuning among GR, GPX and GST in keeping LPO level under control during FeNPs or Hg alone exposure, and a direct role of total GSH (TGSH) in the control of LPO level and impaired GSH metabolism under the concomitant (FeNPs + Hg) exposure. An interpretation of the fish risk to FeNPs in a multi-pollution state should equally consider the potential outcome of the interaction of FeNPs with other contaminants.