Abstract: OBJECTIVE To know the effects of cisplatin combined with magnesium isoglycyrrhizinate on the intervention of progress in mice with primary hepatocellular carcinoma through ERK1/2 signaling pathway and the expression of PGE2 and γδT cells. METHODS Forty-five model mice with primary liver cancer were established and randomly divided into control group, cisplatin group and combined treatment group, each with 15 mice. Normal saline, cisplatin and cisplatin combined with magnesium isoglycyrrhizinate were given intraperitoneally respectively. The therapeutic effects, serum liver function index, prostaglandin E2(PGE2) level, liver nuclear factor-κB(NF-κB) p65, inflammatory factor expression, relative expression of protein on extracellular regulated protein kinases1/2(ERK1/2) and p-ERK1/2, percentage of γδT cells were compared in them. RESULTS The quality of tumor in combination group was lowest, the cisplatin group was higher than that of the combination group, and the control group was the highest(P<0.05). The tumor inhibition rate in the combination group was higher than the cisplatin group(P<0.05). The levels of serum alanine aminotransferase(ALT), aspartate aminotransferase(AST) and PGE2, protein of liver tumor necrosis factor-α(TNF-α), vascular endothelial growth factor(VEGF), NF-κB p65 in the combination group was lowest, the cisplatin group was higher than that of the combination group, and the control group was the highest(P<0.05). There was no difference in the relative protein expression of ERK1/2 among the three groups. The relative expression of p-ERK1/2 protein in live, percentage of γδT cells in the combination group was lowest, the cisplatin group was higher than that of the combination group, and the control group was the highest(P<0.05). CONCLUSION Cisplatin combined with magnesium isoglycyrrhizinate can regulate the ERK1/2 and NF-κB signaling pathway and interfere with the progression of primary liver cancer in mice. It can also reduce the percentage of γδT cells and regulate immune function.