Abstract: Objective To investigate the effects of p70s6k-siRNA on cisplatin-resistant SGC7901/DDP cell line and underlying mechanisms. Methods SGC7901/DDP cells were divided into following groups: a control group, a p70s6k-siRNA transfection group, a DDP group and a combination group of p70s6k-siRNA and DDP. Then, the proliferation of SGC7901/DDP cells in each groups were detected by MTT after corresponding treatment for 24 h, 48 h or 72 h. The levels of P-gp, MRP1 and p-JNK were measured by immunochemical staining and Western blot. The levels of intracellular glutathione (GSH) and MRP1 mRNA were quantified by RT-PCR. The content of GSH and the activity of glutathione S-transferase (GST) were determined. Results Compared with the control group, the p70s6k-siRNA transfection group presented remarkable different inhibitory effects on the proliferation of SGC7901/DDP cells. Meanwhile, the combination group produced statistical different effects against the proliferation of SGC7901/DDP cells, compared with the control and p70s6k-siRNA groups. According to immunochemical and Western blot results, the levels of P-gp, MRP1 and p-JNK obviously decreased in the p70s6k-siRNA and combination groups. The results of RT-PCR showed that the expression of GST and MRP1 mRNA reduced in the p70s6k-siRNA and combination groups. Furthermore, remarkable decreases were found in GSH content and GST activity in the p70s6k-siRNA group, compared with the control group. The GCH content and GST activity in the combination group were significantly lower than those in the control and p70s6k-siRNA groups. Conclusions Transfection of p70s6k-siRNA into SGC7901/DDP cells can inhibit cellular proliferation, and synergic effects can be observed after combination with cisplatin, which may be associated with down-regulation of GSH content, GST activity and the expression of related drug resistance proteins P-gp, MRP1 and p-JNK.