MicroRNAs (miRNAs), a class of non-coding small RNAs, play critical roles in regulating adipocyte biology, including differentiation, proliferation, and lipid metabolism. This study investigates the role of miR-424-3p in adipogenesis. MiR-424-3p expression is dynamically upregulated during adipocyte differentiation. Functional analyses demonstrate that miR-424-3p overexpression suppresses lipid droplet accumulation and coordinately inhibits both anabolic (PPARγ, C/EBPα) and catabolic (ATGL, HSL) pathways; these effects are reversed by co-treatment with a miR-424-3p inhibitor. Lipidomic analysis reveals that miR-424-3p mediates membrane phospholipid remodeling, with significant changes predominantly in glycerophospholipids and sphingolipids, among which PE, PC, and LPE are the major affected species. Together with pathway enrichment analysis, increased lipid reactive oxygen species (ROS) levels, decreased glutathione (GSH) levels, and unaltered cell viability, these results collectively indicate that miR-424-3p may trigger ferroptosis signaling. Mechanistically, we demonstrate that miR-424-3p targets HNRNPA0, thereby upregulating p53 and suppressing ferroptosis inhibitors (SLC7A11, GPX4). HNRNPA0 overexpression reverses these phenotypes, restoring adipocyte metabolism and lipid storage capacity. Our findings establish miR-424-3p as an epigenetic regulator of adipose homeostasis via the HNRNPA0-p53-ferroptosis axis, which constrains lipid accumulation in 3T3-L1 cells. The evolutionary conservation of this mechanism across lipogenically active species highlights its potential as a therapeutic target for obesity-related metabolic disorders.