Abstract: Objective To observe the effect of GSK-3β on the proliferation of human gastric carcinoma cell and its mechanism. Methods Cell proliferation of human gastric carcinoma cell line SGC-7901 treated by LY294002 with or without LiCl was analyzed by MTT assay in vitro.The expression of total GSK-3β,p-GSK-3β^ser9 ,CyclinD1 and Caspase3 was detected by western blotting,RT-PCR and SP immunohistochemistry respectively. Results LY294002 could inhibit the cell proliferation dependent with concentration and time;the expression of total GSK-3β was constant,the protein level of p-GSK-3β^ser9,the CyclinD1mRNA and protein level were down-regulated and the expression of caspase3 was increased after treated SGC-7901 with LY294002 for 72h.The growth inhibition and effect on the expression of CyclinD1 and Caspase3 by the LY294002 were partially abrogated by lithium chloride. Conclusion GSK-3β could negatively regulate the proliferation of human gastric carcinoma cell.The possible mechanism is that GSK-3β could lead to cycle arrest and induce apoptosis.