To further clarify the role of PKA and SHP2 in the anti-HCC effect of IFN-α in vivo, the nude mice bearing Huh-7 HCC cells were established and then treated with IFN-α, SHP2 inhibitor SHP099, PKA inhibitor H89, IFN-α plus SHP099, IFN-α plus H89, respectively. This evidence concerns the gene PTPN11 and hepatocellular carcinoma.