Objective To explore the effect of matrine combined with an Akt signaling pathway inhibitor on theproliferation and apoptosis in renal carcinoma cells in vitro. Methods Renal cell carcinoma ACHN and GRC-1 cells weretreated with different concentrations of matrine, and cell proliferation activity was detected by MTT assay to calculate thehalf inhibitory concentration. Cells treated with a half inhibitory concentration of matrine or an Akt pathway inhibitor werenamed the matrine group and inhibitor group, respectively; cells treated with both were the combined group, and untreatedcells were used as controls. Cell proliferation was detected by MTT, apoptosis was measured by flow cytometry, levels ofreactive oxygen species (ROS) were examined by laser scanning confocal microscopy, and the expression of p38, p-p38,and cleaved caspase-3 was investigated by western blotting. Results Matrine can inhibit the proliferation of renal cancercells in a concentration-dependent manner. Compared with the control group, the cell survival rate decreased, apoptosisrate, ROS level, p-p38 level and cleaved caspase-3 protein level increased in the matrine, inhibitor and combinationgroups. Compared with the matrine group and inhibitor group, the combined group had a lower survival rate, higherapoptosis rate, higher ROS level, higher p-p38 level and cleaved caspase-3 protein level. Conclusions Matrine combinedwith an Akt signaling pathway inhibitor inhibits the proliferation of renal carcinoma cells, and promotes their apoptosis. ROS and p38 signaling pathways may be one of the mechanisms of action of this effect.