Objective To observe the effect of rehmannia glutinosa polysaccharide on STAT3 activity and the its effect on Survivin and the morphological changes, and to explore its role in promoting apoptosis and its impact. Methods H22 hepatocellular carcinoma was transplanted into mice subcutaneously. Fifty solid tumor model mice were randomly divided into 5 groups, treated with different doses of RGP(1 000, 500, 250 mg/kg)ig, cyclophosphamide 40 mg/kg,ip. We studied mice's immune organ index, macrophage function, and inhibition rate. The apoptosis index of tumor cells in each group was determined by the method of TUNEL, and the morphological changes were observed. The expression of STAT3 and Survivin in the tumor was detected by immunohistochemistry. The expression of STAT3 and Survivin protein was detected by Western-blot. Results The inhibitory rates of RGP were 34.76%,45.69%, and 30.32% respectively for the 1 000 mg/kg RGP, 500 mg/kg RGP, and 250 mg/kg RGP groups. Immune organ index(P<0.05)and macrophage function(P<0.05)suggested that RGP could improve the immunity of the body. The apoptotic index of RGP group was significantly higher than that of model group(P<0.01). Immunohistochemical results showed that the expression of STAT3 and Survivin protein in high and low dose group were significantly lower than those in model group(P<0.05). The expression levels of STAT3 and Survivin in medium RGP dose group were significantly lower than that of model group(P<0.01). The results of Western-blot showed that the expression of STAT3 and Survivin protein in medium RGP dose group was significantly different from that of model group(P<0.01). Conclusion RGP can promote cell apoptosis and may to a certain degreeregulate immune function, the mechanism of which may be associated with RGP inhibition of STAT3 signaling pathway, therefore further inhibit the expression of Survivin and other downstream target genes.