The Newcastle disease virus (NDV) M protein is a non-glycosylated membrane-associated protein, which locates on the inner surface of NDV envelope and constitutes the bridge between the viral envelope and the nucleocapsid. Previous studies have shown that the NDV M protein is a nucleocytoplasmic shuttling protein, which plays essential roles in inhibiting host gene transcription and protein synthesis, and also facilitating viral assembly and budding. Up to now, numerous studies have mainly focused on viral F, HN, V proteins and RNP complex to reveal the relationship between the virulence and replication of NDV. However, in recent years, several studies using the reverse genetics techniques have indicated that the M protein is also associated with the virulence and replication of NDV. Therefore, this summary reviews the structural features of M protein, and the relationship between M protein and NDV virulence and replication, which will provide a new theoretical reference for further investigating the functions of NDV M protein.