Abstract: Objective To explore the effect of the demethylation drug 5-Aza-CdR on endometrial carcinoma xenografted in nude mice. Methods Randomly assigned the mice into decitabine (AZA), cisplatin (DDP), medroxyprogesterone acetate (MPA), AZA+DDP, AZA+MPA, DDP+MPA and model groups (three in each group) after building the models of xenografted tumor by transplanting the HEC-1B cells on nude mice, and dealt them respectively with corresponding drugs (1 μg/g, single or combination) in the experiment groups and normal saline in model group (injected per 3 d, 8 injections in total). Then the tumor inhibitory rates in different groups were calculated. The methylation and protein expression of RASSF1A gene was estimated by methylation specific PCR (MSP) and Western blot respectively, and apoptosis situation of carcinoma cell was estimated by tunel. Results Inhibitory rate in AZA + DDP group was the highest, and the lowest was AZA group. RASSF1A gene promoter region methylation levels of AZA, AZA + DDP and AZA + MPA groups significantly reduced and showed obvious demethylation stripes while other groups mainly showed the methylation stripes. The differences of RASSF1A protein expression between AZA, AZA + DDP and AZA + MPA groups were not statistical significant (P>0.05), but the three were higher than model group (P<0.05); there was no statistically significant difference respectively in the DDP, MPA, DDP + MPA groups compared with that of model group (P>0.05). In the comparison of apoptosis index, model group was the lowest, followed by the three single medicine groups, and the highest was three combination groups (P<0.05). Conclusion Demethylation drug 5-Aza-CdR in endometrial cancer treatment has a great potential clinical application value by reversing the abnormal methylation of RASSF1A gene, restoring biological functions of RASSF1A protein and strengthening the efficacy of DDP and MPA.