Newcastle disease virus (NDV) is one of the most significant threats to the poultry industry, and it also exhibits oncolytic properties. In our research, we have identified a non-oncolytic strain, the genotype VII NDV strain I4. We have found that the lack of oncolytic characteristics in this strain is attributed to amino acids 366-489 in the NP protein. To delve into the mechanism of NP-mediated NDV oncolysis, we initiated further investigations using the highly oncolytic Herts/33 strain's NP and a recombinant NP protein with amino acids 366-489 from the I4 strain substituted in (H-NP366-489I). These proteins represent the interacting partners in the proteomics analysis of NP proteins from both viral strains. After infecting HeLa cells with each of these strains, immunoprecipitation was performed using antibodies targeting the NP protein. Since the H-NP366-489I virus produces fewer proteins during replication, we additionally overexpressed the H-NP366-489I and Herts/33 NP proteins separately for immunoprecipitation experiments.