Abstract: This study was to investigate the effect and mechanism of saikosaponin D(SSD)combined with oxaliplatin on nude mice bearing human lung carcinoma A549 cells. The A549 cell-bearing nude mice model was established and then the optimal dosage of SSD for intragastric administration was valued by tumor inhibitory ratio in vivo. The effect of SSD combined with oxaliplatin on tumor growth in A549 cells-bearing nude mice was observed. The apoptosis was detected by TUNEL method, the concentration of prostaglandin E₂(PGE₂)in plasma was checked by ELISA method, and the expression of COX-2 in tumor was analyzed by Western blot. The result showed that SSD exerted best tumor inhibitory effect(40. 96%)at the dosage of 1. 0 mg/kg. SSD combined with oxaliplatin group induced better apoptosis effect in A549 cells-bearing nude mice than those of SSD group and oxaliplatin group, respectively. The concentration of PGE₂ and the expression of COX-2 in model group were increased markedly, while decreased significantly in SSD, oxaliplatin or SSD combined with oxaliplatin treated groups(P< 0. 05), and the concentration of PGE₂ and the expression of COX-2 in SSD combined with oxaliplatin group were significantly lower than those treated by SSD or oxaliplatin alone(P< 0. 01). In conclusion, SSD combined with oxaliplatin could exert synergistic effect to induce apoptosis of A549 cells in nude mice, which may achieved by down-regulation of the expression of COX-2.