Programmed cell death (PCD) refers to a regulated cellular process involving a cascade of biochemical reactions and molecular mechanisms, commonly including apoptosis, necroptosis, and pyroptosis. Ferroptosis is a recently identified form of PCD distinguished by its dependence on iron. Emerging evidence underscores the significance of ferroptosis in viral infections; however, its role in Pseudorabies virus (PRV) infection, an enveloped double-stranded DNA virus belonging to the Alphaherpesvirinae subfamily, remains poorly understood. Here, we demonstrate that PRV infection induces multiple forms of PCD, including ferroptosis, which is characterized by mitochondrial shrinkage, lipid peroxidation, ferrous iron (Fe²) accumulation, and elevated levels of reactive oxygen species (ROS). Ferroptosis facilitates PRV replication, with iron overload playing a crucial role. Mechanistically, we show that transferrin receptor 1 (TfR1) and ferritinophagy are involved in PRV-induced iron overload. Specifically, PRV infection upregulates TfR1 expression via hypoxia-inducible factor-1β (HIF-1β) and promotes its translocation to the cell membrane through Rab11a, thereby enhancing the cellular import of extracellular ferric iron (Fe³). In parallel, PRV activates ferritinophagy to degrade ferritin heavy chain 1 (FTH1) via selective autophagy receptors, nuclear receptor coactivator 4 (NCOA4) and Tax1-binding protein 1 (TAX1BP1), further contributing to intracellular iron accumulation. Altogether, these findings demonstrate that PRV induces ferroptosis by disrupting iron homeostasis through TfR1 activation and ferritinophagy induction, providing novel insights into the pathogenesis of PRV and other herpesviruses.IMPORTANCEFerroptosis is an iron-dependent form of non-apoptotic cell death that primarily involves iron overload, lipid peroxidation, and suppression of antioxidant systems. Increasing evidence indicates that ferroptosis plays an important role in viral infections. In this study, we show that PRV induces ferroptosis by disrupting iron homeostasis through TfR1 activation and ferritinophagy induction. On one hand, PRV infection upregulates TfR1 expression through HIF-1β and facilitates TfR1 translocation to the cell membrane via Rab11a, leading to enhanced import of extracellular Fe into cells. On the other hand, PRV exploits the selective autophagy receptors NCOA4 and TAX1BP1, which strengthens the interaction between NCOA4, TAX1BP1, and FTH1, triggering ferritinophagy and increasing intracellular Fe levels. Collectively, these findings enrich the understanding of the mechanism by which PRV induces ferroptosis, shedding new light on PRV and other alpha-herpesvirus infections.