Newcastle Disease Virus is an avian virus with strong replication ability，which can specifically identify and kill tumor cells. When liver cancer cells are infected with NDV，the apoptosis signaling pathway is activated，inducing apoptosis. USP13 (Ubiquitin Specific Protease 13) is a member of the ubiquitination enzyme family，and deubiquitylate and stabilize PTEN. The expression of USP13 is obviously decreased when NDV infected Huh7 or HLCZ01 cells. USP13 is overexpressed in NDV-infected Huh7 or HLCZ01 cells，which significantly restrains apoptosis. Conversely，knockdown USP13 significantly enhances apoptosis. Further studies revealed the underlying mechanism that USP13 restrains NDV-induced apoptosis. Although overexpression of USP13 doesn't affect NDV replication in two types of liver cancer cells，USP13 can upregulate an important molecule Bcl-2，thereby inhibiting apoptosis. USP13 plays an important role in NDV-induced apoptosis. At the same time，a new theory basis for the oncolytic treatment of liver cancer is provided.