Our results indicated that the ZNF330 protein was involved in the negative regulation of RaMoV replication in the B. tabaci MED. High viral accumulation caused by ZNF330 silencing is detrimental to fecundity and longevity of the B. tabaci MED. These findings provided a new insight into identifying the binding partners in whitefly with viral CP and fully understanding the complex interactions between begomoviruses and their whitefly vector. © 2023 Society of Chemical Industry.