Objective  To investigate the effect of the dual expression plasmid of protein kinase B1(Akt1)-specific siRNA and P53 on the proliferation, migration, invasion and apoptosis of hepatocellular carcinoma (HCC) cells.   Methods  We constructed a dual expression plasmid that co-expressed Akt1-specific siRNA and wild-type p53 gene (pSi-Akt1-P53).The dual expression plasmid pSi-Akt1-P53 was transfected into HepG2 cells of HCC,The expression of Akt1 and P53 was detected by Real-time PCR and Western blotting. Then, the dual expression plasmid was transfected into HepG2 cells, sh-Akt1 plasmid and P53 plasmid were used as control. The effects of the dual plasmid on the proliferation, migration, invasion and apoptosis of HepG2 cells were detected by CCK-8 and 5-ethynyl-2’-deoxyuridine(EdU) experiments, Wound scratch experiment, Transwell chamber experiment and flow cytometry,respectively.   Results  After the dual plasmid was transfected into HepG2 cells, the expression of Akt1 protein was significantly reduced and the expression of P53 protein was significantly increased in HepG2 cells. Compared with the shAkt1 and P53 plasmids, the dual expression plasmid pSi-Akt1-P53 significantly inhibited the proliferation、migration and invasion of HepG2 cells and significantly increased the apoptosis of HepG2 cells.   Conclusion The dual expression plasmid pSi-Akt1-P53 can synergistically inhibit the proliferation, migration and invasion of HepG2 cells, significantly increased the apoptosis of HepG2 cells.