Tomato chlorosis virus (ToCV) is a member of the genus Crinivirus in the family Closteroviridae. It has a wide host range and wide distribution, causing serious harm to the vegetable industry. The autophagy pathway plays an important role in plant resistance to virus infection. Viruses and plant hosts coevolve in defence and antidefence processes around autophagy. In this study, ToCV p22 protein was selected to verify the interaction between ToCV p22 and NbBAG5. Through overexpression and downregulation of NbBAG5, it was found that NbBAG5 could negatively regulate ToCV infection. NbBAG5 was found to be localised in mitochondria and can change the original localisation of ToCV p22, which is colocalised in mitochondria. Further study found that NbBAG5 inhibited the expression of mitophagy-related genes and the number of autophagosomes, thereby regulating viral infection by affecting mitophagy. In summary, this study demonstrated that ToCV p22 affects autophagy by interacting with NbBAG5, established the association between virus infection, BAG proteins family and autophagy pathway and explained the molecular mechanism by which ToCV p22 interacts with NbBAG5 to inhibit autophagy to regulate viral infection.