Background: Neither inactivated vaccine nor attenuated vaccine can effectively prevent and control the infection and spread of Porcine reproductive and respiratory syndrome virus (PRRSV). Therefore, it is necessary to broaden new horizons and conceive effective preventive strategies. Tea polyphenols (TPP) are polyphenol in tea. The main components of TPP are catechins and their derivatives. TPP has many physiological activities, and has certain antiviral and antifungal effects. But whether TPP owns anti-PRRSV activity remains unclear.Results: We found that TPP effectively inhibited PRRSV replication in Marc-145 cells through suppressing viral attachment and internalization. TPP exhibited a potent anti-PRRSV effect regardless of its pre-treatment or post-treatment. In addition, we demonstrated that TPP restrained PRRSV-induced p65 entry into the nucleus to suppress the activation of the NF-κB signaling pathway, which ultimately leads to the inhibition of the expression of inflammatory cytokines. Furthermore, PRRSV limited the synthesis of viral non-structural protein 2 (nsp2), the core component of viral replication transcription complexes, which may contribute to the inhibition of viral RNA replication.Conclusions: TPP has the potential to develop into an effective antiviral agent in PRRSV prevention and control in future.