Objective To investigate the effects of simvatatin on proliferation, apoptosis, the NF-κB signaling pathway in human acute promyelocytic leukemia cell lines NB4. Methods NB4 cells were incubated with different concentration of simvastatin (5 ,10,15 μmol/L) , NB4 cells without any treatment were as control. Cells of different groups were collected at 24, 48 and 72 h after incubation for further detection. MTT method was used to evaluate the growth inhibition rate and flow cytometry was used to detect the early stage apoptosis and necrosis ratio. The human NF-κB signaling pathway RT2 profiler PCR array profiles the expression of genes involved in NF-κB signaling. Results Simvastatin inhibited the proliferation and induced the apoptosis of NB4 cells in time and dose-dependent manner significantly ( all P < 0. 01). The cell growth inhibition rate of NB4 cells treated with 15μmol/L simvastatin were 45. 75% , 92. 91% and 96.46% respectively at 24, 48 and 72 h; and the early stage apoptosis ratio were 30.25% , 64. 34% and 87. 38% , respectively. Compared with the control group, 56 genes expression levels changed in the group of 15 μmol/L simvatatin group at 48 h, among which, 47 genes were down-regulated and 9 genes were up-regulated. Conclusion Simvatatin potentially inhibited proliferation and induce apoptosis of NB4 cells, and the mechanism may be associated with the changes of gene expression levels involved in NF-κB signaling pathway regulated by simvastatin.