Objective: To study the impact of interferon-inducible protein 16 (IFI16) inhibition on apoptosis of human aortic adventitial fibroblasts (HAAFs). Methods: Our research included 3 groups: ① IFI16-siRNA group, specific small interference RNAs (siRNAs) of IFI16 were transfected into HAAFs in vitro to make IFI16 gene silence, ②Con-siRNA group, non-specific siRNAs were transfected into HAAFs as negative control and ③Untreated HAAFs group, blank control. HAAFs cell cycle and apoptosis rate were examined by flow cytometry, IFI16 mRNA expression was measured by real time qRT-PCR, protein expressions of IFI16, p53, p21, Bax and Bcl-2 were detected by Western blot analysis. Results: Compared with Con-siRNA group and Untreated HAAFs group, IFI16-siRNA group showed decreased apoptosis rate of HAAFs (3.33±0.41) % vs (7.42±1.51) % and (6.49±1.10) %, P<0.05, reduced ratio of G0/G1 phase cells (56.64 ± 4.77 ) % vs (69.67±3.54) % and (68.29±4.14) %, P<0.05, while increased ratio of S phase cells (25.23±5.19)% vs (13.76±2.07) % and (14.04±3.00) %, P<0.05. Meanwhile, IFI16-siRNA group presented down-regulated IFI16 mRNA and protein expressions, decreased protein levels of p53, p21, Bax and increased protein level of Bcl-2, all P<0.05. Conclusion: Inhibited IFI16 expression could decrease HAAFs apoptosis, promote cell cycle transition from G1 to S phase which might be related to the suppression of p53/p21 signaling pathway and regulation of Bax/Bcl-2 expression.