Pseudorabies virus (PRV), a member of the Herpesviridae, is the causative agent of an acute infectious disease in a variety of animals. The emergence of a novel variant strain brought huge economic losses to the pig industry since classical vaccine strains were not completely effective against variant strains. Therefore, the development of new anti-pseudorabies virus drugs and vaccines is of great significance for the treatment and prevention of pseudorabies. In this study, we found that germacrone, one of the major components of the essential oils extracted from Rhizoma Curcuma, was able to effectively inhibit PRV replication in a dose-dependent manner in vitro. Germacrone showed antiviral activity against PRV in the early phase of the viral replication cycle. Moreover, we found that germacrone does not directly kill the virus, nor does it affect the expression of the PRV receptor protein nectin-1, nectin-2, and CD155. Our results suggest germacrone could be used as an efficient microbicide or immunomodulatory agent in the control of the emerging variant PRV.