Abstract: Objective To investigate the lethal effect of combination of TMP and 5-Fu in the multidrug resistance of Gastric Carcinoma Cell Lines SGC-7901/ADR. Methods Gastric carcinoma cell lines SGC-7901 and the multidrug resistance cell lines SGC-7901/ADR were considered as target cells, MTT assay was used to investigate the lethal effect of combination of TMP and 5-Fu in vitro,which was observed by Light microscope. Flow cytometer(FCM) was employed to investigate the cell cycles. Results The half inhibition ratio(IC₅₀ ) of 5-Fu against SGC-7901/ ADR was 13. 001 mg/ L, which was reduced to 1. 542mg/ L by 300 mg/ L TMP, The reversal index was 8. 43 ( P < 0. 01) . Malignant cell volume and morphous which exposed to 5-Fu + TMP became smaller and st rinked rounder by Light microscope. FCM revealed that with the effect of 5-Fu + TMP, cell cycle was blocked at presynthetic phase and ambiguous phase-G₀ /G₁ phase and The cells enter the period of DNA synthesis were reduced, inhibition mitosis of SGC-7901/ADR( P < 0. 05) . Conclusion 　Combination of 5-Fu and TMP has st ronger lethal effect against the multidrugs resistance Cell Lines SGC-7901/ ADR in Gast ric Carcinoma, which may provid a new therapeusis against Gast ric Carcinoma.