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Background: Porcine reproductive and respiratory syndrome virus (PRRSV) causes significant economic loss in the swine industry. Currently, there is no effective way to prevent PRRSV infection. Sodium tanshinone IIA sulfonate (STS), a natural compound derived from Salvia miltiorrhiza, was shown to possess anti-PRRSV activity, but the underlying mechanisms remain unclear. The objective of this study was to investigate the effect of STS on PRRSV-induced cell apoptosis and PRRSV N protein expression pattern., Methods: Relative quantification real-time PCR was used to evaluate the inhibition of STS on N gene expression. Simultaneously indirect immunofluorescence assay (IFA) and western blot were used to assess the effect on N protein expression. Apoptosis was analysed using fluorescence microscope with an annexin V-EGFP kit. The effect of STS on caspase-3 cleaving was assessed by western blot., Results: Our results showed that STS could inhibit viral N gene expression at both the messenger RNA stage and at the protein level in PRRSV-infected cells in a dose-dependent manner. In addition, STS could also rescue PRRSV-induced apoptosis., Conclusions: Our data suggest that STS may serve as a base compound for developing more effective drugs against PRRSV infection.