Formaldehyde (FA) has neurotoxic characteristics and causes neurodegenerative disease. Our previous study demonstrated the neuroprotective effects of hydrogen sulfide (H 2 S) on FA-induced neurotoxicity in HT22 cells. Emerging evidence have supported that ferroptosis is involved in FA-induced neurotoxicity. To understand the mechanism of the protection of H 2 S against FA-induced neurotoxicity, this study explored the regulatory effect of H 2 S on FA-induced ferroptosis and the underlying mechanisms. The researcher found that H 2 S (100, 200, and 400 μM, 30 min) reverses the ferroptosis induced by FA (100 μM, 24 h) in HT22 cells (a cell line of mouse hippocampal neurons), including decreases in free iron, reactive oxygen species (ROS), 4-hydroxy-2-trans-nominal (4-HNE), and malondialdehyde (MDA) contents, as well as an increase in glutathione (GSH) content. H 2 S (100, 200, and 400 μM, 30 min) also inhibited ferritinaphagy in FA-exposed HT22 cells, as evidenced by the downregulation of the ferritinophagy receptor nuclear receptor coactivator 4 (NCOA4) and microtubule-associated protein 1 light chain-3B (LC3B) as well as the upregulation of the main iron storage protein ferritin heavy chain 1 (FTH1) and p62. H 2 S (100, 200, and 400 μM, 30 min) also up-regulated the expression of growth differentiation factor-11 (GDF11) in FA-exposed HT22 cells. Furthermore, knockdown of GDF11 in HT22 cells cancelled the beneficial effects of H 2 S in FA-induced ferroptosis and ferritinaphagy. These data indicated that the protective mechanism underlying H 2 S-prevented neurotoxicity of FA is involved in alleviating FA-induced ferroptosis via inhibiting ferritinaphagy by upregulation of GDF11.