Abstract: Objective To investigate the relationship between growth inhibitory effect of arsenic trioxide(As2O3) and phosphorylation of P27kip threonine residue 187(P27T187) in human hepatocellular carcinoma(HCC) cell line SMMC-7721. Methods Cultured in vitro, SMMC-7721 were treated for 72h with 2μmol/L As2O3. The cell growth inhibition was detected by cell number counting and the cell cycle was detected by flow cytometry(FCM).The expression and localization of P27, T187 phosphorylated P27(p-P27T187) were detected by Subcellular Fractionation , Western blot and immunoflurescence. Results As2O3 significantly inhibited the proliferation of SMMC-7721 cell and cell cycle was arrested in G2/M. A striking decrease in p-P27T187 expression and a reciprocal increase in P27 expression were found in 2μmol/L As2O3-treated SMMC-7721 cell. Meanwhile, As2O3 decreased the protein levels of Cdk2 and cyclinE .The location of P27 was transferred from cytoplasm to nuclei and the expression of p-P27T187 was decreased in nuclei. Conclusion As2O3 inhibit the phosphorylation of P27T187, thereby promoting P27 accumulation in SMMC-7721 cell nuclei, inducing cel1 cycle arrest and growth inhibition.