Abstract: Objective To investigate the role of P21 protein and XIAP on apoptosis-inducing effect by mevastatin against A549 cell line and its mechanisms . Methods The cells proliferation were detected by MTT assay . The cell cycle distribution and apoptosis induction were evaluated with flow cytometer and morphologic electron microscope changes. The mRNA expression of p21 and XIAP was measured with reverse transcription-polymerase chain reaction .The protein expression of p21and XIAP were test with flow cytometer and Western Bolt respectively . Results Mevastatin inhibited A549 cell survival in a time-dependent and concentration-depended manner. Flow cytometry show that mevastatin induced G0/G1 phase arrest and caused apoptosis. Mevastatin did not affect P21 expression at both mRNA and total protein level.Concomitantly,P21 protein localized on cellular membrane decreased.Both mRNA and protein expression in XIAP were down regulated by mevastatin . All these effects were reversed by addition of mevalonate . Conclusions Mevastatin can inhibited proliferation ,induce apoptosis and interfere with cell progression of A549 through mevalonate pathway. Its mechanisms involved in decreasing the expression of XIAP mRNA and protern.Targeting HMG-CoA reductase ,Mevastatin blocks the isoprenylation of p21 protein which affects its anchorage on the cellular membrane.