Aim To observe the effect of interferon-inducible protein 204 (p204) on the apoptosis, proliferation and migration of vascular adventitial fibroblast cells (VAF) in rat. Methods The specific small interference RNA (siRNA) of p204 gene (Ifi204) were transfected into VAF in vitro instantaneously. VAF were divided into three groups, Ifi204 siRNA transfection group (Ifi204-siRNA), control siRNA transfection group (Con-siRNA), untreated VAF as a negative intervention control group (Neg). Then the cell vitality to reflect cell proliferation was analyzed by MTT method, cell apoptosis was analyzed by flow cytometry, cell migration by scratch assay and transwell chamber. The mRNA and protein levels of p204, p53 and p21 were measured by real-time qRT-PCR and Western blot, respectively. Results After transfection of the Ifi204 siRNA, the mRNA and protein expression levels of p204, p53 and p21 were decreased in the VAF, and the cell apoptosis was inhibited, the cell proliferation and migration were promoted. Conclusion Inhibition of p204 expression can promote VAF cell growth and migration, which may be related to the inhibition of p53 and p21 expression.