Objective：This study aims to investigate the expression of miR-1301 in hepatocellular carcinoma（HCC） tissues and cell lines，and explore the effect of miR-1301 on the proliferation of HCC cells and its underlying mechanism. Methods：The expression of miR-1301 in HCC tissues，adjacent tissues and cell lines was detected by RT-PCR. CCK-8，and colony formation assay were used to examine proliferation of HCC cells after transfection with miR-1301 mimic or inhibitor. The activity of PI3K，p-AKT and AKT was detected by Western blot. Results：The results showed that the expression of miR-1301 in HCC tissues and HCC cell lines was obviously down-regulated compared with that in the normal controls. RT-PCR showed that the expression of miR-1301 in HCC cells was significantly increased or decreased after miR-1301 mimic or inhibitor transfection（P＜0.01）. Compared with the control，knockdown of miR-1301 could remarkably inhibited the proliferation of Hep3B cells（P＜0.05），while overexpression of miR-1301 presented the opposite effects（P＜0.05）. Furthermore，we found that the activity of PI3K/AKT signal pathway was significantly inhibited by miR-1301. Conclusion：Expression of miR-1301 is low in HCC. The down-regulated miR-1301 in HCC inhibited the proliferation of HCC cells，the underlying mechanisms could be the inhibition of PI3K/AKT signal pathway by miR-1301．