Aim To observe the expression of miR-155 in TNF-α-induced human umbilical vein endothelial cells and the impacts of miR-155 on TNF-α-induced human umbilical vein endothelial cells, and to investigate thoroughly the mechanisms of miR-155 modulating TNF-α-mediated human umbilical vein endothelial cell apoptosis. Methods Human umbilical vein endothelial cells were cultured in vitro and treated with different concentrations of TNF-α for different time. MTT assay was used to detect human umbilical vein endothelial cell activity. Human umbilical vein endothelial cell apoptosis was analysed by Hoechst33342 fluorescence staining and by Annexin-V FITC/PI double staining. The expression of miR-155 was detected by qRT-PCR, the potential apoptosis-related target genes of miR-155 were forecasted by bioinformatics analysis and confirmed by Western blot. Results TNF-α induced human umbilical vein endothelial cell apoptosis in a dose-dependent and time-dependent manner. Compared with the vehicle control, miR-155 expression increased obviously in human umbilical vein endothelial cells treated with 10 μg/L TNF-α at 24 h (P＜0.01). Over-expression of miR-155 significantly promoted the proliferation of TNF-α-induced human umbilical vein endothelial cells and decreased remarkably their apoptosis (P＜0.01). Interestingly, this effect was obviously reversed in the introduction of the anti-miR-155. Bioinformatics analysis revealed that FADD and Caspase-3 were the potential apoptosis-related target genes of miR-155. Western blot demonstrated that miR-155 negatively regulated Caspase pathways by inhibiting the expression of target genes FADD and Caspase-3. MTT assay and Annexin V-FITC/PI double staining indicated that silencing of Caspase pathways enhanced the pro-proliferation and anti-apoptotic effect of miR-155. Conclusion MiR-155 inhibits TNF-α-induced human umbilical vein endothelial cell apoptosis through down-regulating FADD and Caspase-3 expression.