Heterogeneous nuclear ribonucleoproteins (hnRNPs) are a family of RNA-binding proteins that play crucial roles in RNA processing, transcriptional regulation, nucleocytoplasmic transport, and apoptosis. As a member of the hnRNP family, heterogeneous nuclear ribonucleoprotein M (hnRNPM) has been implicated in diverse cellular processes, including the regulation of tumor-associated gene expression, promotion of angiogenesis, enhancement of tumor cell invasion and metastasis, and modulation of RNA virus replication. However, the interaction between hnRNPM and pseudorabies virus (PRV) remains unexplored. In this study, we demonstrated that hnRNPM overexpression in PK15 and 3D4/21 cells significantly inhibited PRV replication, whereas hnRNPM knockdown enhanced viral replication. Although PRV infection did not alter total cellular hnRNPM levels, it induced the nuclear translocation of hnRNPM. Mechanistically, hnRNPM promoted apoptosis in PRV-infected cells by upregulating the expression of cleaved caspase-3, -6, and -7, as well as Bax, while downregulating Bcl-2. This apoptosis induction consequently suppressed PRV replication. Furthermore, hnRNPM was found to colocalize with caspase-6. Our findings reveal that hnRNPM inhibits PRV replication by inducing apoptosis in infected cells. These results not only enhance our understanding of PRV-host interactions but also highlight hnRNPM as a promising therapeutic target for the development of antiviral strategies against PRV.