Porcine reproductive and respiratory syndrome virus (PRRSV) is one of the most economically important pathogens to the swine industry worldwide over the past three decades. No approved effective antiviral drug is available to control this virus. The antiviral effects of allicin (diallyl thiosulfinate) on many human and animal viruses have been documented. However, the antiviral effect of allicin on PRRSV infection remains unknown. In this study, we found that allicin exhibited an inhibitory effect on HP-PRRSV and NADC30-like PRRSV in a dose-dependent manner by interfering with viral entry, replication, and assembly. Furthermore, allicin alleviated the expression of pro-inflammatory cytokines (IFN-β, IL-6, and TNFα) induced by PRRSV infection. The pro-inflammatory signaling pathways, TNF signaling pathway and MAPK signaling pathway, up-regulated by PRRSV infection were restored by allicin treatment. Taken together, these results demonstrate that allicin has antiviral activity against PRRSV and ameliorates inflammatory responses induced by PRRSV infection, suggesting that allicin is a promising drug candidate for anti-PRRSV therapy in vivo.