Viruses have developed a variety of methods to evade host immune response. Our previous study showed that infectious bursal disease virus (IBDV) inhibited type I interferon production via interaction of VP4 with cellular glucocorticoid-induced leucine zipper (GILZ) protein. However, the exact underlying molecular mechanism is still unclear. In this study, we found that IBDV VP4 suppressed GILZ degradation by inhibiting K48-linked ubiquitylation of GILZ. Furthermore, mutation of VP4 (R41G) abolished the inhibitory effect of VP4 on IFN-beta expression and GILZ ubiquitylation, indicating that the amino acid 41R of VP4 was required for the suppression of IFN-beta expression and GILZ ubiquitylation. Moreover, IBDV infection or VP4 expression markedly inhibited endogenous GILZ ubiquitylation. Thus, IBDV VP4 suppresses type I interferon expression by inhibiting K48-linked ubiquitylation of GILZ, revealing a new mechanism employed by IBDV to suppress host response.