AIM: To study the effect of Fas on cisplatin resistance in stomach cancer cells and its possible mechanisms.METHODS: The expression of Fas at mRMA and protein levels in SGC-7901 cells and SGC-7901 /DDP cells was determined by RT-qPCR and Western blot.Fas-containing adenovirus vector was transfected into the SGC-7901 /DDP cells to upregulate Fas expression.The cell viability was detected by CCK-8 assay.The cell cycle and cell apoptosis were analyzed by flow cytometry.The protein levels of Fas, P38 /p-P38, JNK/p-JNK, cleaved caspase-8/caspase-8 and cleaved caspase-3 /caspase-3 were detected by Western blot.RESULTS: The expression of Fas at both mRNA and protein levels was significantly downregulated in the SGC-7901 /DDP cells.Fas expression was decreased by cisplatin in a dose-dependent manner in the SGC-7901 cells.Overexpression of Fas suppressed the viability and induced apoptosis in the SGC-7901 /DDP cells, and upregulated the protein levels of p-P38, p-JNK, cleaved caspase-8 and cleaved caspase-3.CONCLUSION:Overexpression of Fas increases the sensitivity of the SGC-7901 /DDP cells to cisplatin, and inhibits the cell growth and promotes cell apoptosis.The mechanism may be related to the activation of JNK and P38 pathway.