Objective To explore the effects of the expression changes of SH2 domain-containing protein tyrosine phosphatase 2 (SHP2) on the proliferation of human hepatic stellate cells LX-2 and the PI3K/Akt signaling pathway.〖WTHZ〗Methods Using adenovirus as the vector, the wild-type SHP2 gene and the shRNA targeting SHP2 were introduced into LX-2 cells. LX-2 cells were divided into the Control group (transfection of LX-2 cells with DMEM medium instead of adenovirus), the Ad-GFP group (transfection of LX-2 cells with empty virus Ad-GFP), the Ad-shRNA/SHP2 group (transfection of LX-2 cells with adenovirus carrying the shRNA targeting SHP2), and the Ad-SHP2 group (transfection of LX-2 cells with adenovirus carrying the wild-type SHP2). Real-time fluorescence quantitative PCR and Western blot were used to detect the expression of SHP2 and Akt in LX-2 cells. The CCK-8 method was used to detect the proliferation of LX-2 cells. Western blot was used to detect the expression of phosphorylated Akt (p-Akt) in LX-2 cells. Results The exogenous wild-type SHP2 gene and shRNA targeting SHP2 were successfully introduced into LX-2 cells, and the expressions of SHP2 in LX-2 cells were upregulated and downregulated (P＜0.05). Overexpression of SHP2 significantly increased the proliferation and expression of p-Akt (P＜0.05), while low expression of SHP2 significantly reduced the proliferation and expression of p-Akt in LX-2 cells (P＜0.05). Nevertheless, overexpression and low expression of SHP2 had no significant effect on the expression of Akt protein and mRNA in LX-2 cells (P＞0.05). Conclusion Overexpression of SHP2 promotes the proliferation, while low expression of SHP2 leads to a decrease of the proliferation in LX-2 cell. The PI3K/Akt signaling pathway mediates the regulation of SHP2 on the proliferation in LX-2 cell